{"database":"Pride","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Txt":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/05/PXD057088/checksum.txt"],"Other":["ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/05/PXD057088/FE543DAB1_A1_Slot1-50_1_23242.d.zip","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/05/PXD057088/FE543DAB1_B1_Slot1-53_1_23246.d.zip","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/05/PXD057088/FE543DAB1_A2_Slot1-51_1_23243.d.zip","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/05/PXD057088/FE543DAB1_B2_Slot1-54_1_23247.d.zip","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/05/PXD057088/FE543DAB1_A3_Slot1-52_1_23244.d.zip","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/05/PXD057088/result.zip","ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/05/PXD057088/FE543DAB1_B3_Slot2-1_1_23248.d.zip"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"labhead_mail":["rounphy0723@163.com"],"submitter":["Fei Yuan"],"technology_type":["Data-dependent acquisition","Mass Spectrometry"],"disease":["Acute Kidney Failure"],"software":[""],"submitter_keywords":["Extracellular vesicles","Mesenchymal stromal cells","Anti-oxidative stress","Renal ischemia reperfusion injury","Hypoxia pretreated"],"full_dataset_link":["https://www.ebi.ac.uk/pride/archive/projects/PXD057088"],"tissue":["Mesenchymal Cell"],"sample_protocol":["The normoxic and hypoxic EVs samples were prepared and analyzed in triplicates (n=3). The primary experimental procedures for proteomics analysis include protein extraction, trypsin digestion, liquid chromatograph mass spectrometer (LC-MS/MS) analysis and data analysis."],"repository":["Pride"],"quantification_method":[""],"modification":[""],"data_protocol":["The resulting MS/MS data were processed using the DIA-NN search engine (Version 1.8). Tandem mass spectra were searched against the Human UniProt database (20376 entries) concatenated with a reverse decoy database. Subcellular localization analysis of the differentially expressed protein in MSC-EV was identified by PSORTbsoftware (v3.0). Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used for KEGG pathway enrichment analysis. Reactome pathway annotation and WikiPathways pathway annotations were identified by Reactome database and WikiPathways database. The proteomics analysis in our research is supported by Jingjie PTM BioLabs."],"omics_type":["Proteomics"],"labhead":["Fei Yuan"],"instrument_platform":[""],"labhead_affiliation":["Shanghai Children Medical Center, School of Medicine, Shanghai Jiao Tong University"],"submission_type":["PARTIAL"],"species":["Homo Sapiens (human)"],"publication":["39901252 Yuan F, Liu J, Zhong L, Liu P, Li T, Yang K, Gao W, Zhang G, Sun J, Zou X. Enhanced therapeutic effects of hypoxia-preconditioned mesenchymal stromal cell-derived extracellular vesicles in renal ischemic injury. Stem Cell Res Ther. 2025 16(1):39 10.1186/s13287-025-04166-z"],"submitter_mail":["roundphy0723@163.com"],"submitter_affiliation":["Shanghai Children Medical Center, School of Medicine, Shanghai Jiao Tong University"],"submitter_country":["China"],"pubmed_abstract":["<h4>Background</h4>Extracellular vesicles (EVs) secreted by mesenchymal stromal cells (MSCs) have been shown to provide significant protection against renal ischemia-reperfusion injury (IRI). Hypoxia has emerged as a promising strategy to enhance the tissue repair capabilities of MSCs. However, the specific effects of hypoxia on MSCs and MSC-EVs, as well as their therapeutic potential in renal IRI, remain unclear. In this study, we investigated the alterations occurring in MSCs and the production of MSC-EVs following hypoxia pre-treatment, and further explored the key intrinsic mechanisms underlying the therapeutic effects of hypoxic MSC-EVs in the treatment of renal IRI.<h4>Methods</h4>Human umbilical cord MSCs were cultured under normoxic and hypoxic conditions. Proliferation and related pathways were measured, and RNA sequencing was used to detect changes in the transcriptional profile. MSC-EVs from both normoxic and hypoxic conditions were isolated and characterized. In vivo, the localization and therapeutic effects of MSC-EVs were assessed in a rat renal IRI model. Histological examinations were conducted to evaluate the structure, proliferation, and apoptosis of IRI kidney tissue respectively. Renal function was assessed by measuring serum creatinine and blood urea nitrogen levels. In vitro, the therapeutic potential of MSC-EVs were measured in renal tubular epithelial cells injured by antimycin A. Protein sequencing analysis of hypoxic MSC-EVs was performed, and the depletion of Glutathione S-Transferase Omega 1 (GSTO1) in hypoxic MSC-EVs was carried out to verify its key role in alleviating renal injury.<h4>Results</h4>Hypoxia alters MSCs transcriptional profile, promotes their proliferation, and increases the production of EVs. Hypoxia-pretreated MSC-EVs demonstrated a superior ability to mitigate renal IRI, enhancing proliferation and reducing apoptosis of renal tubular epithelial cells both in vivo and in vitro. Protein profiling of the EVs revealed an accumulation of numerous anti-oxidative stress proteins, with GSTO1 being particularly prominent. Knockdown of GSTO1 significantly reduced the antioxidant and therapeutic effects on renal IRI of hypoxic MSC-EVs.<h4>Conclusions</h4>Hypoxia significantly promotes the generation of MSC-EVs and enhances their therapeutic effects on renal IRI. The antioxidant stress effect induced by GSTO1 is identified as one of the most critical underlying mechanisms. Our findings highlight that hypoxia-pretreated MSC-EVs represent a novel and promising therapeutic strategy for renal IRI."],"pubmed_title":["Enhanced therapeutic effects of hypoxia-preconditioned mesenchymal stromal cell-derived extracellular vesicles in renal ischemic injury."],"pubmed_authors":["Yuan Fei F, Liu Jie J, Zhong Liang L, Liu Pengtao P, Li Ting T, Yang Kexin K, Gao Wei W, Zhang Guangyuan G, Sun Jie J, Zou Xiangyu X"],"sample_synonyms":["liquid chromatography tandem mass spectroscopy, LC-MS2, PRSS, LCMSMS, determination, Analyses, Peptidomics, protein complex, Proteins, beta-Trypsin, LC-MS/MS, Tripcellim, Gene, proteins, protein, protein-containing complex, beta Trypsin, LC-MS-MS, Protein Gene Products, Gene Proteins, Trypure, data analysis, protein polypeptide chains, LC/MS/MS, data processing, native protein, natural protein, polypeptide chain, Data, liquid chromatography-tandem mass spectroscopy, chemical analysis, Protein, LC-MSMS, Gene Products, liquid chromatography tandem mass spectrometry, liquid, Data Analyses., assay, Analysis, protein aggregate"],"pubmed_abstract_synonyms":["SCR, Rat, PhrB photolyase activity, RNA Sequence Determination, Laboratory, Sequence Determination, RNA Sequence, Stem Cells, Stromal Cells, Physical, Mesenchymal Stromal Cells, Glandular, Norway Rats, trauma, Oxygen Deficiencies, scr, rat, protein polypeptide chains, Oxidative DNA, Oxidative, Method, Programmed, symptoms, 3, 5-dioxonan-7-yl ester, NUP96, establishment and maintenance of substrate location, Nitro-Oxidative Stresses, Analysis, BHLHA22, epithelium, 5-dihydro-4H-imidazol-4-one, DNA Damage, Multipotent Mesenchymal Stromal Cells, treatment, Theory, Utility Theories, Analyses, Blood Urea, creatinina, Tissue, Salt, GSTX, Oxidative Cleavage, Economic Policies, Bone Marrow Stromal Stem Cells, Adenomatous Epithelial, proteins, Living Costs, procedures, Amino Acid Sequence Analysis, Sequence Determinations, SUPPRESSOR OF AUXIN RESISTANCE 3, Oxygen, Intrinsic Pathway Apoptosis, Oxidative Stresses, scientific observation, Reperfusion Damage, birth cord, Role Concepts, marrow stromal cells, Household Consumptions, Economic, Virosin, SPG-R, 2(or 3)-methyl-, 3-((3-(formylamino)-2-hydroxybenzoyl)amino)-8-hexyl-2, reniculate kidney, screening, Sulfate Salt, Indices, Index, Myor, Injury and Wounds, Antioxidants, Aptitudes, ABF1, Endogenous, Mesenchymal Progenitor Cells, Physical Traumas, Test, Squamous, Procedure, Umbilical, DmIKKgamma, Economic Condition, Mesenchymal Stromal Cell, signaling (initiator) caspase activity, Role Concept, Rattus norwegicus, induction of apoptosis, MYOR, MyoR, Utility Theory, dIKK, Role, dipyrimidine photolyase (photosensitive), MscS, Gstx, simple tissue, Macroeconomic, DNA Oxidative Damages, Caspase-Dependent, Therapeutic Effect, Ischemia-Reperfusion Injuries, Reperfusion Damages, Adenomatous Epithelial Cells, Adipose-Derived Mesenchymal Stem Cells, mesenchymal stromal cells, Adipose Tissue Derived Mesenchymal Stromal Cells, Consumer Price Indices, IKK-gamma, signs, Methodological, rats, Home, human, Adipose-Derived Mesenchymal Stromal Cells, Adipose Derived, Condition, Intrinsic Pathway Apoptoses, Protein Sequence, Nitro-Oxidative, Gtsttl, Nitrogen, 2-amino-1, tube like, Cells, Extrinsic Pathway, Research-Related Injuries, Adipose Tissue Derived Mesenchymal Stem Cell, Protein Sequence Determinations, DNA, Anoxemia, humans, establishment and maintenance of cellular component location, Oxidative Damage, Research Related Injuries, Policies, Mesenchymal Stem Cell, conformation, In Vitro as Topic, Apoptotic Body, Effects, Antioxidative, Endogenous Antioxidant, Utility, antioxydant, Wharton's Jelly Cells, fam:GSTomega, Ischemia-Reperfusion Injury, apoptotic programmed cell death, protein-containing complex, Injuries and Wounds, dIKK-gamma, activation of apoptosis, Easterlin, Human, stem cells, Oxygen Deficiency, In Vitro Testing, Peptide Sequence Determinations, Rats, Wounds, Stromal Cell, DmIKK-gamma, Gene Products, Ischemia-Reperfusion, Wharton's Jelly Cell, mesenchymal stromal cell, Technique, Man, Protein Sequence Determination, Oxidative Damages, In Vitro Tests, In, Injury, DmScr, 1-methylglycocyamidine, Creatinine Sulfate, Reperfusion, F23A5.3, Microeconomic Factors, Sequencing, Creatinine, 5-dihydro-1-methyl-4H-Imidazol-4-one, Study, Peptide Sequence, Abilities, Use, Antipiricullin, Capital, Transitional Epithelial Cells, Antioxidative Stresses, Classic Apoptosis, Extracellular, execution phase of apoptotic process, Antioxidant Activity, Protein Sequence Analysis, CG1030, Bone Marrow Mesenchymal Stem Cell, Sequence Analyses, Apoptosis, Transitional, measuring, Squamous Cells, RNA, cell suicide, findings, RNA Sequence Determinations, Conditions, Progenitor Cells, apoptotic cell death, 9-dioxo-1, Proteins, Factor, function, Anti-oxidative Stresses, tube-shaped, Cell, Vesicle, Concept, IKKgamma, disease management., In Vitro Test, Cuboidal Glandular Epithelial Cells, native protein, Consumer Price Index, Consumer Price, traumatic injury, Wounds and Injury, Oxidative Nitrative Stresses, Laboratory Rats, Trauma, Antioxidant Effect, Amino Acid Sequence Determination, chemical analysis, bHLHa22, Columnar Glandular Epithelial Cells, Kreatinin, Vitro Testing, DmelCG1030, Bone Marrow Stromal Cell, RPE, Anti-oxidative Stress, apoptosis, DNA Oxidative Damage, underdeveloped, Dmikkgamma, Ischemia Reperfusion Injury, Protein Sequence Analyses, wound, Peptide Sequence Determination, CG16910, Body, p. pigmentosa retinae, Classic Apoptoses, Gene Proteins, Adipose Tissue-Derived Mesenchymal Stem Cells, Deficiency, localisation, apoptotic program, Talent, Multipotent, In Vitro Technique, Stress, commitment to apoptosis, deoxyribonucleate pyrimidine dimer lyase (photosensitive), Norway, DNA Oxidative, Anti Oxidants, Therapeutic Effects, Epithelial Cell, Activity, determination, Wound, Blood, Norway Rat, Nitrative Stress, yolk stalk, Extracellular Vesicle, Multipotent Mesenchymal Stromal Cell, protein, Serum, pigmented epithelium, type I programmed cell death, injury, Damage, Techniques, tubulate, Peptide Sequence Analysis, Extrinsic Pathway Apoptoses, Roles, Mammals, Nitro-Oxidative Stress, Protein Sequencing, Concepts, antimycin A1b, Norway rat, Umbilical Cords, protein aggregate, Oxidative Injury, mesenchymal precursor cell, Microeconomic, Effect, IKKg, Research-Related, KEY, Key, Anti Oxidant, Oxidative Injuries, Man (Taxonomy), AA407097, Household Consumption, Determination, pigmented retina, hypoplasia, mesenchymal, Oxidative DNA Damages, CFU-F, BUN, DNA cyclobutane dipyrimidine photolyase activity, Anti-oxidative, Laboratory Rat, Bone Marrow Mesenchymal Stem Cells, Oxidative Stress Injuries, Methodological Studies, Whartons Jelly Cells, Classic, Antioxidant, Therapeutic Use, Classical Apoptosis, disease management, Anti-Oxidant Effect, Therapies, Theories, 1-Methylhydantoin-2-imide, Transitional Epithelial Cell, Therapy, PRE, establishment and maintenance of substance location, cellular suicide, Home Economics, Caspase-Dependent Apoptosis, Hypothesis, deoxyribonucleic cyclobutane dipyrimidine photolyase activity, Modern, Adenomatous, Rattus, P28, Blood Serum, Adipose Tissue-Derived Mesenchymal Stem Cell, Transitional Epithelial, Anti-Oxidants, Macroeconomic Factors, funiculus umbilicalis, Determinations, Economics, Ability, 1-Methylglycocyamidine, single organism localization, Mus norvegicus, Household, colony-forming unit-fibroblast, Stem Cell, Reperfusion Injuries, retinal pigment, Intrinsic Pathway, Oxidative and Nitrosative Stress, Extrinsic Pathway Apoptosis, Apoptotic, Kenny, Physical Trauma, p28, connecting stalk, retinal pigment layer, Adenomatous Epithelial Cell, Antimycin A1, Amino Acid, Adipose-Derived, Squamous Cell, antioxidants, Factors, In Vitro, Tests, Hypoxemia, Cell Death, Adipose Tissue Derived Mesenchymal Stem Cells, Methodological Study, Treatments, mesenchymal stem cell, AI194287, Kidneys, phr A photolyase activity, AU018802, Endogenous Antioxidants, DNA-photoreactivating enzyme, DmelCG16910, Easterlin Hypothesis, induction of apoptosis by p53, Mesenchymal Progenitor Cell, Mesenchymal, Adipose Derived Mesenchymal Stromal Cells, Creatine anhydride, Oxidative Stress Injury, Research-Related Injury, Bone Marrow Stromal Cells, Classical, Apoptoses, Sequence Analysis, Remittances, Multipotent Bone Marrow Stromal Cells, Amino Acid Sequence Determinations, Oxidative Stress, GSTTLP28, human being, Exovesicles, Procedures, norvegicus, Testings, Bodies, Mesenchymal Stem Cells, antoxidant, Deficiencies, caspase-dependent programmed cell death, Progenitor Cell, Vesicles, Antioxidative Stress, Adipose Tissue Derived Mesenchymal Stromal Cell, Caspase Dependent Apoptosis, Gene, cyclic nucleotide-regulated small mechanosensitive ion channel, Amino Acid Sequencing, Glandular Epithelial, Ischemia Reperfusion, photoreactivating enzyme activity, ABF-1, bone marrow stromal cells, Stresses, Fintrol, Rattus sp. strain Wistar, Squamous Epithelial Cells, Oxidative Nitrative, Homo sapiens, polypeptide chain, reduced, Stress Injury, Anti-Oxidant, Studies, establishment and maintenance of position, Creatinine Sulfate Salt, Oxidative Cleavages, Wharton Jelly Cells, stratum pigmentosa retinae, dmIKKgamma, Rattus rattiscus, tiny, Type I, Anti-Oxidant Effects, IKK[[gamma]], Hypoxia, Squamous Epithelial, Epithelial, brown rat, study, Adipose Tissue-Derived Mesenchymal Stromal Cells, Adipose Derived Mesenchymal Stem Cells, MOS3, deoxyribocyclobutadipyrimidine pyrimidine-lyase activity, Rattus norvegicus, PRECOCIOUS, BG:DS07876.2, mesenchymal progenitor cells, Economic Conditions, apoptosis activator activity, 2-Amino-1-methylimidazolin-4-one, MSC, Msc, chorda umbilicalis, GSTTLp28, IKK, Anti oxidative Stress, RNA Sequence Analyses, Epithelial Cells, Oxidative DNA Damage, Traumas, Urea Nitrogen, RNA Sequencing, programmed cell death by apoptosis, Squamous Epithelial Cell, relational structural quality, Adipose Derived Mesenchymal Stem Cell, F23A5_3, Glandular Epithelial Cell, Rattus norvegicus8, Policy, small, Economic Policy, conditioned mesenchymal stem cell, GSTO 1-1, Adipose-Derived Mesenchymal Stem Cell, 6-dimethyl-4, Krebiozen, l(3)84Af, protein complex, Apoptotic Bodies, Cords, Production, 2-Amino-1-methyl-1, Living Cost, Peptide, Anti Oxidant Effect, Cord, Testing, Consumption, Anoxia, HEL-S-21, Oxidative Nitrative Stress, MODIFIER OF SNC1, natural protein, Programmed Cell Death, Protein, deoxyribonucleic photolyase activity, In Vitro Testings, establishment and maintenance of localization, techniques, Acid Sequencing, Peptide Sequence Analyses, Exovesicle, apoptosis signaling, Anti Oxidant Effects, BMSC, Uses, Butanoic acid, photolyase activity, Multipotent Bone Marrow Stromal Cell, Glandular Epithelial Cells, Adipose Tissue-Derived Mesenchymal Stromal Cell, Talents, single-organism localization, Amino, Cleavage, Amino Acid Sequence Analyses, Injuries, Protein Gene Products, Antioxidant Effects, Remittance, Therapeutic, Cost of Living, Modern Man, RNA Sequence Analysis, Treatment, assay, Nitro Oxidative Stress, Serums, methodology, Gunn rats"],"name_synonyms":["Research Related Injuries, Multipotent Bone Marrow Stromal Cells, Mesenchymal Stem Cell, Therapeutic Effects, Exovesicles, Effects, Apoptotic Body, Bodies, Wound, Mesenchymal Stem Cells, Deficiencies, Stem Cells, Progenitor Cell, Stromal Cells, Physical, Vesicles, Mesenchymal Stromal Cells, Adipose Tissue Derived Mesenchymal Stromal Cell, Wharton's Jelly Cells, Multipotent Mesenchymal Stromal Cell, Extracellular Vesicle, injury, Injuries and Wounds, bone marrow stromal cells, trauma, Oxygen Deficiency, Oxygen Deficiencies, stem cells, Wounds, Stromal Cell, Wharton Jelly Cells, Hypoxia, mesenchymal precursor cell, Effect, Wharton's Jelly Cell, mesenchymal stromal cell, Research-Related, Multipotent Mesenchymal Stromal Cells, Adipose Tissue-Derived Mesenchymal Stromal Cells, Adipose Derived Mesenchymal Stem Cells, Injury, mesenchymal progenitor cells, mesenchymal, Bone Marrow Stromal Stem Cells, CFU-F, MSC, Oxygen, Bone Marrow Mesenchymal Stem Cells, Use, Whartons Jelly Cells, Traumas, Extracellular, Therapeutic Use, marrow stromal cells, Bone Marrow Mesenchymal Stem Cell, Adipose Derived Mesenchymal Stem Cell, Adipose-Derived Mesenchymal Stem Cell, Injury and Wounds, Progenitor Cells, Apoptotic Bodies, Mesenchymal Progenitor Cells, Physical Traumas, Adipose Tissue-Derived Mesenchymal Stem Cell, Vesicle, Anoxia, Mesenchymal Stromal Cell, colony-forming unit-fibroblast, Stem Cell, traumatic injury, Wounds and Injury, Trauma, Apoptotic, Physical Trauma, Therapeutic Effect, Exovesicle, Bone Marrow Stromal Cell, Uses, Adipose-Derived, BMSC, Adipose-Derived Mesenchymal Stem Cells, mesenchymal stromal cells, Adipose Tissue Derived Mesenchymal Stromal Cells, Multipotent Bone Marrow Stromal Cell, wound, Hypoxemia, Adipose Tissue-Derived Mesenchymal Stromal Cell, Adipose Tissue Derived Mesenchymal Stem Cells, Body, Injuries, Adipose-Derived Mesenchymal Stromal Cells, Adipose Derived, MSC cell, mesenchymal stem cell, Injuries., Adipose Tissue-Derived Mesenchymal Stem Cells, Deficiency, Therapeutic, Mesenchymal Progenitor Cell, Multipotent, Mesenchymal, Adipose Derived Mesenchymal Stromal Cells, Research-Related Injuries, Adipose Tissue Derived Mesenchymal Stem Cell, Research-Related Injury, Anoxemia, Bone Marrow Stromal Cells"],"description_synonyms":["SCR, Rat, PhrB photolyase activity, RNA Sequence Determination, Laboratory, Sequence Determination, RNA Sequence, Stem Cells, Stromal Cells, Physical, Mesenchymal Stromal Cells, Glandular, Norway Rats, trauma, Oxygen Deficiencies, scr, rat, protein polypeptide chains, Oxidative DNA, Oxidative, Method, Programmed, symptoms, 3, 5-dioxonan-7-yl ester, NUP96, establishment and maintenance of substrate location, Nitro-Oxidative Stresses, Analysis, BHLHA22, epithelium, 5-dihydro-4H-imidazol-4-one, DNA Damage, Multipotent Mesenchymal Stromal Cells, treatment, Theory, Utility Theories, Analyses, Blood Urea, creatinina, Tissue, Salt, GSTX, Oxidative Cleavage, Economic Policies, Bone Marrow Stromal Stem Cells, Adenomatous Epithelial, proteins, Living Costs, procedures, Amino Acid Sequence Analysis, Sequence Determinations, SUPPRESSOR OF AUXIN RESISTANCE 3, Oxygen, Intrinsic Pathway Apoptosis, Oxidative Stresses, Reperfusion Damage, birth cord, Role Concepts, marrow stromal cells, Household Consumptions, Economic, Virosin, SPG-R, transcription from bacterial-type RNA polymerase promoter, 2(or 3)-methyl-, 3-((3-(formylamino)-2-hydroxybenzoyl)amino)-8-hexyl-2, reniculate kidney, screening, Sulfate Salt, Indices, Index, Myor, Injury and Wounds, Antioxidants, Aptitudes, ABF1, Endogenous, Mesenchymal Progenitor Cells, Physical Traumas, Test, Squamous, Procedure, Umbilical, DmIKKgamma, Economic Condition, Mesenchymal Stromal Cell, signaling (initiator) caspase activity, Role Concept, Rattus norwegicus, induction of apoptosis, MYOR, MyoR, Utility Theory, dIKK, Role, dipyrimidine photolyase (photosensitive), MscS, Gstx, simple tissue, Macroeconomic, DNA Oxidative Damages, Caspase-Dependent, Therapeutic Effect, Ischemia-Reperfusion Injuries, Reperfusion Damages, Adenomatous Epithelial Cells, Adipose-Derived Mesenchymal Stem Cells, mesenchymal stromal cells, Adipose Tissue Derived Mesenchymal Stromal Cells, Consumer Price Indices, IKK-gamma, signs, Methodological, rats, Home, human, Adipose-Derived Mesenchymal Stromal Cells, Adipose Derived, Condition, Intrinsic Pathway Apoptoses, Protein Sequence, Nitro-Oxidative, Gtsttl, Nitrogen, 2-amino-1, tube like, Cells, Extrinsic Pathway, Research-Related Injuries, Adipose Tissue Derived Mesenchymal Stem Cell, Protein Sequence Determinations, DNA, Anoxemia, humans, establishment and maintenance of cellular component location, Oxidative Damage, Research Related Injuries, Policies, Mesenchymal Stem Cell, conformation, In Vitro as Topic, Apoptotic Body, Effects, Antioxidative, Endogenous Antioxidant, Utility, antioxydant, Wharton's Jelly Cells, fam:GSTomega, Ischemia-Reperfusion Injury, apoptotic programmed cell death, protein-containing complex, Injuries and Wounds, dIKK-gamma, activation of apoptosis, Easterlin, Human, stem cells, Oxygen Deficiency, In Vitro Testing, Peptide Sequence Determinations, Rats, Wounds, Stromal Cell, DmIKK-gamma, Gene Products, Ischemia-Reperfusion, Wharton's Jelly Cell, mesenchymal stromal cell, Technique, Man, Protein Sequence Determination, Oxidative Damages, In Vitro Tests, In, Injury, DmScr, 1-methylglycocyamidine, interventionDescription, Creatinine Sulfate, Reperfusion, F23A5.3, Microeconomic Factors, Sequencing, Creatinine, 5-dihydro-1-methyl-4H-Imidazol-4-one, Study, Peptide Sequence, Abilities, Use, Antipiricullin, Capital, Transitional Epithelial Cells, Antioxidative Stresses, SURGICAL AND MEDICAL PROCEDURES., Classic Apoptosis, Extracellular, execution phase of apoptotic process, Antioxidant Activity, Protein Sequence Analysis, CG1030, Bone Marrow Mesenchymal Stem Cell, Sequence Analyses, Apoptosis, Transitional, Squamous Cells, RNA, cell suicide, findings, RNA Sequence Determinations, Conditions, Progenitor Cells, apoptotic cell death, 9-dioxo-1, Proteins, Factor, function, Anti-oxidative Stresses, tube-shaped, Cell, Vesicle, Concept, IKKgamma, In Vitro Test, Cuboidal Glandular Epithelial Cells, native protein, Consumer Price Index, Consumer Price, traumatic injury, Wounds and Injury, Oxidative Nitrative Stresses, Laboratory Rats, Trauma, Antioxidant Effect, Amino Acid Sequence Determination, chemical analysis, bHLHa22, Columnar Glandular Epithelial Cells, Kreatinin, Vitro Testing, Intervention, DmelCG1030, Bone Marrow Stromal Cell, RPE, Anti-oxidative Stress, apoptosis, DNA Oxidative Damage, underdeveloped, Dmikkgamma, Ischemia Reperfusion Injury, Protein Sequence Analyses, wound, Peptide Sequence Determination, CG16910, Body, p. pigmentosa retinae, plan specification, Classic Apoptoses, Gene Proteins, Adipose Tissue-Derived Mesenchymal Stem Cells, Deficiency, localisation, apoptotic program, Talent, Multipotent, In Vitro Technique, Stress, commitment to apoptosis, deoxyribonucleate pyrimidine dimer lyase (photosensitive), Norway, DNA Oxidative, Anti Oxidants, Therapeutic Effects, Epithelial Cell, Activity, determination, Wound, Blood, Norway Rat, Nitrative Stress, yolk stalk, Extracellular Vesicle, Multipotent Mesenchymal Stromal Cell, protein, Serum, pigmented epithelium, type I programmed cell death, injury, Damage, Techniques, tubulate, Peptide Sequence Analysis, Extrinsic Pathway Apoptoses, Roles, Mammals, Nitro-Oxidative Stress, Protein Sequencing, Concepts, antimycin A1b, Norway rat, Umbilical Cords, protein aggregate, Oxidative Injury, mesenchymal precursor cell, Microeconomic, Effect, IKKg, Research-Related, KEY, Key, Anti Oxidant, Oxidative Injuries, Man (Taxonomy), AA407097, Household Consumption, Determination, pigmented retina, hypoplasia, mesenchymal, Oxidative DNA Damages, CFU-F, BUN, DNA cyclobutane dipyrimidine photolyase activity, Anti-oxidative, Laboratory Rat, Bone Marrow Mesenchymal Stem Cells, Oxidative Stress Injuries, Methodological Studies, Whartons Jelly Cells, Classic, Antioxidant, Therapeutic Use, Classical Apoptosis, disease management, Anti-Oxidant Effect, Therapies, Theories, 1-Methylhydantoin-2-imide, Transitional Epithelial Cell, Therapy, PRE, establishment and maintenance of substance location, cellular suicide, Home Economics, Caspase-Dependent Apoptosis, Hypothesis, deoxyribonucleic cyclobutane dipyrimidine photolyase activity, Modern, Adenomatous, Rattus, P28, Blood Serum, Adipose Tissue-Derived Mesenchymal Stem Cell, Transitional Epithelial, Anti-Oxidants, Macroeconomic Factors, funiculus umbilicalis, Determinations, Economics, Ability, 1-Methylglycocyamidine, single organism localization, Mus norvegicus, Household, colony-forming unit-fibroblast, Stem Cell, Reperfusion Injuries, retinal pigment, Intrinsic Pathway, Oxidative and Nitrosative Stress, Extrinsic Pathway Apoptosis, Apoptotic, Kenny, Physical Trauma, p28, connecting stalk, retinal pigment layer, Adenomatous Epithelial Cell, Antimycin A1, Amino Acid, Adipose-Derived, Squamous Cell, antioxidants, Factors, In Vitro, Tests, Hypoxemia, Cell Death, Adipose Tissue Derived Mesenchymal Stem Cells, Methodological Study, Treatments, mesenchymal stem cell, AI194287, Kidneys, phr A photolyase activity, AU018802, Endogenous Antioxidants, DNA-photoreactivating enzyme, DmelCG16910, Easterlin Hypothesis, induction of apoptosis by p53, Mesenchymal Progenitor Cell, bacterial transcription, Mesenchymal, Adipose Derived Mesenchymal Stromal Cells, Creatine anhydride, Oxidative Stress Injury, Research-Related Injury, Bone Marrow Stromal Cells, Classical, Apoptoses, Sequence Analysis, Remittances, Multipotent Bone Marrow Stromal Cells, Amino Acid Sequence Determinations, Oxidative Stress, GSTTLP28, human being, Exovesicles, Procedures, norvegicus, Testings, Bodies, Mesenchymal Stem Cells, antoxidant, Deficiencies, caspase-dependent programmed cell death, Progenitor Cell, Vesicles, Antioxidative Stress, Adipose Tissue Derived Mesenchymal Stromal Cell, Caspase Dependent Apoptosis, Gene, cyclic nucleotide-regulated small mechanosensitive ion channel, Amino Acid Sequencing, Glandular Epithelial, Ischemia Reperfusion, photoreactivating enzyme activity, ABF-1, bone marrow stromal cells, Stresses, Intervention or Procedure, Fintrol, method, Rattus sp. strain Wistar, Squamous Epithelial Cells, Oxidative Nitrative, Homo sapiens, polypeptide chain, reduced, Stress Injury, method used in an experiment, Anti-Oxidant, Studies, establishment and maintenance of position, Creatinine Sulfate Salt, Oxidative Cleavages, Wharton Jelly Cells, stratum pigmentosa retinae, dmIKKgamma, Rattus rattiscus, tiny, Type I, Anti-Oxidant Effects, IKK[[gamma]], Hypoxia, Squamous Epithelial, Epithelial, brown rat, study, Adipose Tissue-Derived Mesenchymal Stromal Cells, Adipose Derived Mesenchymal Stem Cells, MOS3, deoxyribocyclobutadipyrimidine pyrimidine-lyase activity, Rattus norvegicus, PRECOCIOUS, BG:DS07876.2, mesenchymal progenitor cells, Interventional, Economic Conditions, apoptosis activator activity, 2-Amino-1-methylimidazolin-4-one, MSC, Msc, chorda umbilicalis, GSTTLp28, IKK, Anti oxidative Stress, RNA Sequence Analyses, Epithelial Cells, Oxidative DNA Damage, Traumas, Urea Nitrogen, RNA Sequencing, programmed cell death by apoptosis, Squamous Epithelial Cell, relational structural quality, Adipose Derived Mesenchymal Stem Cell, F23A5_3, Glandular Epithelial Cell, Rattus norvegicus8, Policy, small, Economic Policy, Intervention Strategies, conditioned mesenchymal stem cell, GSTO 1-1, Adipose-Derived Mesenchymal Stem Cell, 6-dimethyl-4, Krebiozen, l(3)84Af, protein complex, Apoptotic Bodies, Cords, Production, 2-Amino-1-methyl-1, Living Cost, Peptide, Anti Oxidant Effect, Cord, Testing, Consumption, Anoxia, HEL-S-21, Oxidative Nitrative Stress, MODIFIER OF SNC1, natural protein, Programmed Cell Death, Protein, deoxyribonucleic photolyase activity, In Vitro Testings, establishment and maintenance of localization, techniques, Acid Sequencing, Peptide Sequence Analyses, Exovesicle, apoptosis signaling, Anti Oxidant Effects, BMSC, Uses, Butanoic acid, photolyase activity, Multipotent Bone Marrow Stromal Cell, Glandular Epithelial Cells, Adipose Tissue-Derived Mesenchymal Stromal Cell, Talents, single-organism localization, Amino, Cleavage, Amino Acid Sequence Analyses, Injuries, Protein Gene Products, Antioxidant Effects, Remittance, Therapeutic, Cost of Living, Modern Man, RNA Sequence Analysis, Treatment, assay, Nitro Oxidative Stress, Serums, methodology, Gunn rats"],"data_synonyms":["SCR, posttranslational modification, human being, Materials, Activity, determination, Peptidomics, Laboratory, FBN, Gene, protein, protein-containing complex, ABF-1, Human, bone marrow stromal cells, scr, protein polypeptide chains, Homo sapiens, polypeptide chain, ECTOL1, establishment and maintenance of position, Gene Products, establishment and maintenance of substrate location, BHLHA22, Research Activity, protein aggregate, Laboratory Research, Man, WMS, Priorities, Search Engines, posttranslational amino acid modification, Man (Taxonomy), DmScr, Genetic, Genomes, Research, MS2, BG:DS07876.2, proteins, posttranslational protein modification, MSC, Msc, OCTD, marrow stromal cells, CG1030, Development and Research, Research Priority, GPHYSD2, SGS, establishment and maintenance of substance location, conditioned mesenchymal stem cell, Encyclopedias, l(3)84Af, Myor, protein complex, T5E21.12, Modern, Proteins, ABF1, Research Priorities, Search, Cistrons, Engine, ACMICD, single organism localization, Priority, native protein, natural protein, colony-forming unit-fibroblast, MYOR, MyoR, chemical analysis, Protein, bHLHa22, Research Activities, Genetic Materials, MFS1, establishment and maintenance of localization, tandem MS, Genetic Material, WMS2, Data Base, T5E21_12, Research and Development, DmelCG1030, BMSC, PTM, MS/MS, MASS, single-organism localization, post-translational amino acid modification., human, Protein Gene Products, Activities, Gene Proteins, localisation, Material, post-translational modification, Modern Man, SSKS, Cistron, assay, humans, establishment and maintenance of cellular component location"],"pubmed_title_synonyms":["Research Related Injuries, Multipotent Bone Marrow Stromal Cells, Mesenchymal Stem Cell, Therapeutic Effects, Exovesicles, Effects, Apoptotic Body, Bodies, Wound, Mesenchymal Stem Cells, Deficiencies, Stem Cells, Progenitor Cell, Stromal Cells, Physical, Vesicles, Mesenchymal Stromal Cells, Adipose Tissue Derived Mesenchymal Stromal Cell, Wharton's Jelly Cells, Multipotent Mesenchymal Stromal Cell, Extracellular Vesicle, injury, Injuries and Wounds, bone marrow stromal cells, trauma, Oxygen Deficiency, Oxygen Deficiencies, stem cells, Wounds, Stromal Cell, Wharton Jelly Cells, Hypoxia, mesenchymal precursor cell, Effect, Wharton's Jelly Cell, mesenchymal stromal cell, Research-Related, Multipotent Mesenchymal Stromal Cells, Adipose Tissue-Derived Mesenchymal Stromal Cells, Adipose Derived Mesenchymal Stem Cells, Injury, mesenchymal progenitor cells, mesenchymal, Bone Marrow Stromal Stem Cells, CFU-F, MSC, Oxygen, Bone Marrow Mesenchymal Stem Cells, Use, Whartons Jelly Cells, Traumas, Extracellular, Therapeutic Use, marrow stromal cells, Bone Marrow Mesenchymal Stem Cell, Adipose Derived Mesenchymal Stem Cell, Adipose-Derived Mesenchymal Stem Cell, Injury and Wounds, Progenitor Cells, Apoptotic Bodies, Mesenchymal Progenitor Cells, Physical Traumas, Adipose Tissue-Derived Mesenchymal Stem Cell, Vesicle, Anoxia, Mesenchymal Stromal Cell, colony-forming unit-fibroblast, Stem Cell, traumatic injury, Wounds and Injury, Trauma, Apoptotic, Physical Trauma, Therapeutic Effect, Exovesicle, Bone Marrow Stromal Cell, Uses, Adipose-Derived, BMSC, Adipose-Derived Mesenchymal Stem Cells, mesenchymal stromal cells, Adipose Tissue Derived Mesenchymal Stromal Cells, Multipotent Bone Marrow Stromal Cell, wound, Hypoxemia, Adipose Tissue-Derived Mesenchymal Stromal Cell, Adipose Tissue Derived Mesenchymal Stem Cells, Body, Injuries, Adipose-Derived Mesenchymal Stromal Cells, Adipose Derived, MSC cell, mesenchymal stem cell, Injuries., Adipose Tissue-Derived Mesenchymal Stem Cells, Deficiency, Therapeutic, Mesenchymal Progenitor Cell, Multipotent, Mesenchymal, Adipose Derived Mesenchymal Stromal Cells, Research-Related Injuries, Adipose Tissue Derived Mesenchymal Stem Cell, Research-Related Injury, Anoxemia, Bone Marrow Stromal Cells"],"additional_accession":[]},"is_claimable":false,"name":"Enhanced Therapeutic Effects of Hypoxia-Preconditioned Mesenchymal Stromal Cell-Derived Extracellular Vesicles in Renal Ischemic Injury","description":"Background Extracellular vesicles (EVs) secreted by mesenchymal stromal cells (MSCs) provide significant protection against renal ischemia-reperfusion injury (IRI). Hypoxia is considered an important method for enhancing the tissue repair capabilities of MSCs. However, the specific effects of hypoxia on MSCs and MSC-EVs, as well as their therapeutic potential for renal IRI, remain unclear. In this study, we investigated the alterations in MSCs and the production of MSC-EVs following hypoxia pre-treatment, and further explored the key intrinsic mechanisms by which hypoxic MSC-EVs treat renal IRI. Methods Human umbilical cord MSCs were cultured under normoxic and hypoxic conditions. Proliferation and related pathways were measured, and RNA sequencing was used to detect changes in the transcription profile. MSC-EVs from both normoxic and hypoxic conditions were isolated and characterized. In vivo, the localization and therapeutic effects of MSC-EVs were assessed in a rat renal IRI model. Histological examinations were employed to assess the structure, proliferation, and apoptosis of IRI kidney tissue respectively. Renal function was measured by analyzing serum creatinine and blood urea nitrogen levels. In vitro, the therapeutic potential of MSC-EVs were measured in renal tubular epithelial cells injured by antimycin A. Protein sequencing analysis of hypoxic MSC-EVs was conducted, and the depletion of Glutathione S-Transferase Omega 1 (GSTO1) in hypoxic MSC-EVs was performed to verify its key role in alleviating renal injury. Results Hypoxia alters MSCs transcription, promotes their proliferation, and increases the production of EVs. Hypoxia-pretreated MSC-EVs exhibited a superior ability to mitigate renal IRI, enhancing proliferation and reducing apoptosis of renal tubular epithelial cells both in vivo and in vitro. Protein profiling of the EVs revealed an accumulation of numerous anti-oxidative stress proteins, with GSTO1 being particularly prominent. GSTO1 knock down was significantly reduced the antioxidant and therapeutic effects in renal IRI of hypoxic MSC-EVs. Conclusions Hypoxia significantly promotes MSC-EVs generation and enhances the therapeutic effect of EVs on renal IRI. The effect of antioxidant stress induced by GSTO1 is one of the most important underlying mechanisms. Our findings underscore that hypoxia-pretreated MSC-EVs represent a novel and promising therapeutic intervention for renal IRI.","dates":{"publication":"2025-05-07","submission":"2024-10-23"},"accession":"PXD057088","cross_references":{"TAXONOMY":["NEWT:330879","NEWT:377960","NEWT:1131","NEWT:35795","NEWT:2042546","NEWT:259447","NEWT:295546","NCBITaxon:2719036","NEWT:1334565","NEWT:625351","NEWT:258594","NCBITaxon:1280","NEWT:112503","NEWT:1129","NEWT:309807","NEWT:59753","NEWT:89184","NEWT:309800","NEWT:281395","NEWT:247480","NEWT:1211601","NEWT:876138","NEWT:44271","NEWT:193516","NEWT:2315688","NEWT:592321","NEWT:1073882","NEWT:6819","NEWT:475174","NEWT:111205","NEWT:1599","NEWT:428386","NEWT:1117","NEWT:498257","NEWT:10036","NEWT:32264","NEWT:12215","NEWT:1590","NEWT:10034","NEWT:33114","NEWT:1596","NEWT:661410","NEWT:638632","NEWT:224326","NEWT:294671","NEWT:376619","NEWT:1748418","NCBITaxon:79857","NEWT:1096976","NEWT:3765","NEWT:3767","NEWT:1589","NEWT:135622","NEWT:4615","NEWT:672127","NEWT:35786","NEWT:1580","NEWT:399784","NEWT:96731","NEWT:656064","NEWT:1582","NEWT:3760","NEWT:1584","NEWT:2086595","NEWT:36630","NEWT:1585","NEWT:383379","NEWT:381198","NEWT:418106","NCBITaxon:12721","NEWT:166340","NEWT:10029","NEWT:913645","NEWT:2492962","NEWT:641809","NEWT:1392488","NEWT:38815","NEWT:317447","NEWT:4688","NEWT:3357","NEWT:111225","NEWT:7719","NEWT:29073","NEWT:5530","NEWT:868565","NEWT:135674","NEWT:1562698","NEWT:79329","NEWT:30069","NEWT:12637","NEWT:59729","NEWT:2164133","NEWT:295105","NEWT:108061","NEWT:60711","NEWT:2020713","NEWT:224308","NEWT:3347","NEWT:49928","NEWT:3349","NEWT:160621","NEWT:2502409","NEWT:212790","NEWT:110368","NEWT:55350","NEWT:1916073","NEWT:1310161","NEWT:77133","NEWT:145481","NEWT:1310165","NEWT:29058","NCBITaxon:79824","NEWT:1912919","NEWT:410658","NEWT:5516","NEWT:44688","NEWT:44689","NEWT:370038","NEWT:498211","NEWT:345076","NEWT:347256","NEWT:5518","NEWT:398007","NEWT:1527468","NEWT:498217","NEWT:498216","NEWT:11320","NEWT:246196","NEWT:246197","NEWT:145458","NEWT:1310173","NEWT:200795","NEWT:342808","NEWT:2579791","NEWT:44685","NEWT:161934","NEWT:156587","NEWT:1148","NEWT:5508","NEWT:3329","NEWT:419481","NEWT:5507","NEWT:260499","NEWT:410661","NEWT:329854","NEWT:1140","NCBITaxon:2157","NEWT:2066563","NEWT:2649329","NEWT:1143","NEWT:1287689","NEWT:1094343","NEWT:1462472","NEWT:1336795","NEWT:644042","NEWT:150808","NEWT:1182590","NEWT:3712","NEWT:3711","NEWT:3714","NCBITaxon:37162","NEWT:270643","NEWT:3715","NEWT:1538","NEWT:2065263","NEWT:199225","NEWT:177437","NEWT:717966","NEWT:10891","NEWT:10418","NEWT:118698","NEWT:1616117","NEWT:118696","NEWT:34865","NEWT:52283","NEWT:28174","NEWT:284812","NEWT:8175","NEWT:43330","NEWT:1603293","NEWT:44664","NEWT:43346","NEWT:3702","NEWT:1245466","NEWT:3704","NEWT:244366","NEWT:1246791","NEWT:176597","NEWT:118694","NEWT:2850","NEWT:118691","NEWT:34871","NEWT:9006","NEWT:33548","NEWT:52299","NEWT:8165","NEWT:96794","NEWT:10886","NEWT:3708","NEWT:332648","NEWT:44670","NEWT:926571","NEWT:536231","NEWT:376219","NEWT:219813","NEWT:1510","NEWT:1955249","NEWT:460519","NEWT:1515","NEWT:572307","NEWT:1432138","NEWT:2714896","NEWT:1424507","NEWT:1194599","NEWT:272844","NEWT:1348799","NEWT:1608994","NEWT:33995","NEWT:55784","NEWT:1303443","NEWT:9483","NEWT:485","NEWT:56636","NEWT:2709072","NEWT:2499525","NEWT:1122981","NEWT:2853422","NEWT:1122984","NEWT:487","NEWT:1538553","NEWT:1679718","NEWT:480","NEWT:67767","NEWT:45972","NEWT:46835","NEWT:109757","NEWT:582580","NEWT:1185650","NEWT:216778","NEWT:294607","NEWT:1502","NEWT:128017","NEWT:2836","NEWT:376686","NEWT:237610","NEWT:95486","EFO:0001352","NEWT:119562","NEWT:1883446","NEWT:31345","NEWT:1233435","NEWT:118223","NEWT:11757","NEWT:987059","NEWT:109760","NEWT:29031","NEWT:317047","NEWT:1509","NEWT:491","NEWT:460523","NEWT:45954","NEWT:235443","NEWT:1579","NEWT:1757312","NEWT:85694","NEWT:109786","NEWT:1922344","NEWT:108458","NEWT:5936","NEWT:85692","NEWT:321967","NEWT:320637","NEWT:1078283","NEWT:3750","NEWT:983964","NEWT:11706","NEWT:32644","NEWT:527796","NEWT:279010","NEWT:499175","NEWT:109779","NEWT:3745","NEWT:1715989","NCBITaxon:4751","NEWT:3747","NEWT:1116234","NEWT:415978","NEWT:235455","NEWT:1255228","NEWT:410289","NEWT:191701","NEWT:373153","NEWT:1640278","NEWT:9054","NEWT:472","NEWT:940825","NEWT:29459","NEWT:529507","NEWT:1071661","NEWT:1380096","NEWT:28128","NEWT:470","NEWT:41122","NEWT:5911","NEWT:1328300","NEWT:748693","NCBITaxon:50557","NEWT:39251","NEWT:29491","NEWT:101841","NEWT:446","NEWT:153481","NEWT:2014887","NEWT:717989","NEWT:33952","NEWT:11723","NEWT:445","NEWT:153009","NEWT:261756","NEWT:166314","NEWT:166313","NEWT:63366","NEWT:63367","NEWT:29488","NEWT:1871049","NEWT:215402","NEWT:1547","NEWT:1290454","NEWT:3726","NEWT:906914","NEWT:81231006","NEWT:30455","NEWT:28141","NEWT:9031","NEWT:27292","NEWT:1050722","NEWT:3728","NEWT:108931","NEWT:1293497","NEWT:1055524","NEWT:548","NEWT:150475","NEWT:267872","NEWT:381666","NEWT:172269","NEWT:9534","NEWT:2126348","NEWT:5180","NEWT:256737","NEWT:299467","NEWT:9541","NEWT:51350","NEWT:8694","NEWT:33936","NEWT:8692","NEWT:542","NEWT:2903","NEW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