Thrombin-reduced miR-27b attenuates platelet angiogenic activities via enhancing platelet de novo synthesis of anti-angiogenic thrombospondin-1
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE96533 | GEO | 2017/03/14
SECONDARY ACCESSION(S): PRJNA378945
REPOSITORIES: GEO
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Project description:Background and Aims: Recent studies have implicated platelets, particularly α-granules, in the development of steatohepatitis (NASH). However, the specific mechanisms involved have yet to be determined. Notably, thrombospondin 1 (TSP1) is a major component of the platelet α-granules released during platelet activation. The role of platelet-derived TSP1 in NASH remains unknown and was investigated in this study. Approach and Results: Platelet-specific TSP1 knockout mice (TSP1Δpf4) and their wild type littermates (TSP1F/F) were used. NASH was induced by feeding the mice a diet enriched in fat, sucrose, fructose, and cholesterol (AMLN diet). A human liver NASH organoid model was also employed. Although TSP1 deletion in platelets did not affect diet-induced steatosis, TSP1Δpf4 mice exhibited attenuated NASH and liver fibrosis, accompanied by improvements in plasma glucose and lipid homeostasis. Moreover, intrahepatic platelet accumulation, activation and chemokine production were reduced in TSP1Δpf4 mice, which was correlated with decreased immune cell infiltration into the liver. Consequently, this leads to diminished pro-inflammatory signaling in the liver and mitigated the progression of NAFLD. Moreover, in vitro data revealed that co-culturing TSP1-deficient platelets in a human liver NASH organoid model attenuated hepatic stellate cell activation and NASH progression. Additionally, TSP1 deficient platelets play a role in regulating brown fat endocrine function, specifically affecting Nrg4 production. Crosstalk between brown fat and the liver may also influence NAFLD progression. Conclusions: These data suggest that platelet α-granule-derived TSP1 is a significant contributor to diet-induced NASH and fibrosis, and may serve as a new therapeutic target for this severe liver disease.
2024-03-13 | GSE250004 | GEO
Project description:Thrombin-reduced miR-27b attenuates platelet angiogenic activities via enhancing platelet de novo synthesis of anti-angiogenic thrombospondin-1
| PRJNA378945 | ENA
Project description:MicroRNAs (miRNAs) regulate cell physiology by altering protein expression, but the biology of platelet miRNAs is largely unexplored. We tested whether platelet miRNA levels were associated with platelet reactivity by genome-wide profiling using platelet RNA from 19 healthy subjects. We found that human platelets express 284 miRNAs. Unsupervised hierarchical clustering of miRNA profiles resulted in 2 groups of subjects that appeared to cluster by platelet aggregation phenotypes. Seventy-four miRNAs were differentially expressed (DE) between subjects grouped according to platelet aggregation to epinephrine, a subset of which predicted the platelet reactivity response. Using whole genome mRNA expression data on these same subjects, we computationally generated a high-priority list of miRNA-mRNA pairs in which the DE platelet miRNAs had binding sites in 3'UTRs of DE mRNAs, and the levels were negatively correlated. Three miRNA-mRNA pairs (miR-200b:PRKAR2B, miR-495:KLHL5 and miR-107:CLOCK) were selected from this list and all 3 miRNAs knocked down protein expression from the target mRNA. Reduced activation from platelets lacking PRKAR2B supported these findings. In summary, (1) platelet miRNAs are able to repress expression of platelet proteins, (2) miRNA profiles are associated with and may predict platelet reactivity, and (3) bioinformatic approaches can successfully identify functional miRNAs in platelets. Total RNA from the platelets of 19 donors was harvested and labeled with Hy3. Reference RNA (a pool of all samples) was labeled with Hy5. This submission represents the miRNA expression component of the study.
2011-09-26 | E-GEOD-27917 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) regulate cell physiology by altering protein expression, but the biology of platelet miRNAs is largely unexplored. We tested whether platelet miRNA levels were associated with platelet reactivity by genome-wide profiling using platelet RNA from 19 healthy subjects. We found that human platelets express 284 miRNAs. Unsupervised hierarchical clustering of miRNA profiles resulted in 2 groups of subjects that appeared to cluster by platelet aggregation phenotypes. Seventy-four miRNAs were differentially expressed (DE) between subjects grouped according to platelet aggregation to epinephrine, a subset of which predicted the platelet reactivity response. Using whole genome mRNA expression data on these same subjects, we computationally generated a high-priority list of miRNA-mRNA pairs in which the DE platelet miRNAs had binding sites in 3'UTRs of DE mRNAs, and the levels were negatively correlated. Three miRNA-mRNA pairs (miR-200b:PRKAR2B, miR-495:KLHL5 and miR-107:CLOCK) were selected from this list and all 3 miRNAs knocked down protein expression from the target mRNA. Reduced activation from platelets lacking PRKAR2B supported these findings. In summary, (1) platelet miRNAs are able to repress expression of platelet proteins, (2) miRNA profiles are associated with and may predict platelet reactivity, and (3) bioinformatic approaches can successfully identify functional miRNAs in platelets.
2011-09-27 | GSE27917 | GEO
Project description:Impact of high platelet turnover on the platelet transcriptome: Results from platelet RNA-sequencing in patients with sepsis
| PRJEB45262 | ENA
Project description:Objective Circular RNAs (circRNAs) are covalently closed, endogenous non-coding RNAs. CircRNAs play a vital role in liver diseases, acting as microRNA (miRNA) sponges. However, the angiogenic role of circRNA remains unknown in liver fibrosis and is the focus of this study. Methods Liver fibrosis was induced by thioacetamide (TAA), or carbon tetrachloride (CCl4) in mice. CircRNA-microarray, AGO2-RNA immunoprecipitation (RIP), and RNA-seq were utilized to explore the hepatic circRNAs profile. The qPCR and PCR-gel electrophoresis analysis were used to investigate the characterization of circRNA-007371. Liver tissues and EMOA murine endothelial cells were used to verify the angiogenic mechanism of circRNA-007371. Results The increased collagen deposition, pseudolobule formation, and angiogenesis were observed in murine liver induced by TAA and CCl4. CircRNA-microarray in TAA-induced fibrotic murine liver indicated that the expression of circRNA-007371 was up-regulated. Moreover, AGO2-RIP and PCR analysis showed that circRNA-007371 had the characterization of circRNAs and played a role as competing endogenous RNAs (ceRNA) sponging miR-200a. In vitro, circRNA-007371 promoted the ability of migration, growth, and blood vessel formation in EMOA murine endothelial cells using wound healing and tube formation assay. The AGO2-RIP and RNA-sequencing analysis in overexpression circRNA-007371 EMOA murine endothelial cells demonstrated that circRNA-007371 upregulates the stromal antigen 1 (Stag1) via spouse of miR-200a and HIF-1 signaling pathway might participate in the angiogenesis. Conclusions This study discovers that circRNA-007371, a novel ceRNA, is up-regulated, and enhances the angiogenesis via angiocrine role to regulate the STAG1-miR-200a-5p signaling pathway in liver fibrosis.
2023-06-28 | GSE218579 | GEO
Project description:Objective Circular RNAs (circRNAs) are covalently closed, endogenous non-coding RNAs. CircRNAs play a vital role in liver diseases, acting as microRNA (miRNA) sponges. However, the angiogenic role of circRNA remains unknown in liver fibrosis and is the focus of this study. Methods Liver fibrosis was induced by thioacetamide (TAA), or carbon tetrachloride (CCl4) in mice. CircRNA-microarray, AGO2-RNA immunoprecipitation (RIP), and RNA-seq were utilized to explore the hepatic circRNAs profile. The qPCR and PCR-gel electrophoresis analysis were used to investigate the characterization of circRNA-007371. Liver tissues and EMOA murine endothelial cells were used to verify the angiogenic mechanism of circRNA-007371. Results The increased collagen deposition, pseudolobule formation, and angiogenesis were observed in murine liver induced by TAA and CCl4. CircRNA-microarray in TAA-induced fibrotic murine liver indicated that the expression of circRNA-007371 was up-regulated. Moreover, AGO2-RIP and PCR analysis showed that circRNA-007371 had the characterization of circRNAs and played a role as competing endogenous RNAs (ceRNA) sponging miR-200a. In vitro, circRNA-007371 promoted the ability of migration, growth, and blood vessel formation in EMOA murine endothelial cells using wound healing and tube formation assay. The AGO2-RIP and RNA-sequencing analysis in overexpression circRNA-007371 EMOA murine endothelial cells demonstrated that circRNA-007371 upregulates the stromal antigen 1 (Stag1) via spouse of miR-200a and HIF-1 signaling pathway might participate in the angiogenesis. Conclusions This study discovers that circRNA-007371, a novel ceRNA, is up-regulated, and enhances the angiogenesis via angiocrine role to regulate the STAG1-miR-200a-5p signaling pathway in liver fibrosis.
2023-06-28 | GSE218578 | GEO
Project description:Objective Circular RNAs (circRNAs) are covalently closed, endogenous non-coding RNAs. CircRNAs play a vital role in liver diseases, acting as microRNA (miRNA) sponges. However, the angiogenic role of circRNA remains unknown in liver fibrosis and is the focus of this study. Methods Liver fibrosis was induced by thioacetamide (TAA), or carbon tetrachloride (CCl4) in mice. CircRNA-microarray, AGO2-RNA immunoprecipitation (RIP), and RNA-seq were utilized to explore the hepatic circRNAs profile. The qPCR and PCR-gel electrophoresis analysis were used to investigate the characterization of circRNA-007371. Liver tissues and EMOA murine endothelial cells were used to verify the angiogenic mechanism of circRNA-007371. Results The increased collagen deposition, pseudolobule formation, and angiogenesis were observed in murine liver induced by TAA and CCl4. CircRNA-microarray in TAA-induced fibrotic murine liver indicated that the expression of circRNA-007371 was up-regulated. Moreover, AGO2-RIP and PCR analysis showed that circRNA-007371 had the characterization of circRNAs and played a role as competing endogenous RNAs (ceRNA) sponging miR-200a. In vitro, circRNA-007371 promoted the ability of migration, growth, and blood vessel formation in EMOA murine endothelial cells using wound healing and tube formation assay. The AGO2-RIP and RNA-sequencing analysis in overexpression circRNA-007371 EMOA murine endothelial cells demonstrated that circRNA-007371 upregulates the stromal antigen 1 (Stag1) via spouse of miR-200a and HIF-1 signaling pathway might participate in the angiogenesis. Conclusions This study discovers that circRNA-007371, a novel ceRNA, is up-regulated, and enhances the angiogenesis via angiocrine role to regulate the STAG1-miR-200a-5p signaling pathway in liver fibrosis.
2023-06-28 | GSE218577 | GEO
Project description:Objective Circular RNAs (circRNAs) are covalently closed, endogenous non-coding RNAs. CircRNAs play a vital role in liver diseases, acting as microRNA (miRNA) sponges. However, the angiogenic role of circRNA remains unknown in liver fibrosis and is the focus of this study. Methods Liver fibrosis was induced by thioacetamide (TAA), or carbon tetrachloride (CCl4) in mice. CircRNA-microarray, AGO2-RNA immunoprecipitation (RIP), and RNA-seq were utilized to explore the hepatic circRNAs profile. The qPCR and PCR-gel electrophoresis analysis were used to investigate the characterization of circRNA-007371. Liver tissues and EMOA murine endothelial cells were used to verify the angiogenic mechanism of circRNA-007371. Results The increased collagen deposition, pseudolobule formation, and angiogenesis were observed in murine liver induced by TAA and CCl4. CircRNA-microarray in TAA-induced fibrotic murine liver indicated that the expression of circRNA-007371 was up-regulated. Moreover, AGO2-RIP and PCR analysis showed that circRNA-007371 had the characterization of circRNAs and played a role as competing endogenous RNAs (ceRNA) sponging miR-200a. In vitro, circRNA-007371 promoted the ability of migration, growth, and blood vessel formation in EMOA murine endothelial cells using wound healing and tube formation assay. The AGO2-RIP and RNA-sequencing analysis in overexpression circRNA-007371 EMOA murine endothelial cells demonstrated that circRNA-007371 upregulates the stromal antigen 1 (Stag1) via spouse of miR-200a and HIF-1 signaling pathway might participate in the angiogenesis. Conclusions This study discovers that circRNA-007371, a novel ceRNA, is up-regulated, and enhances the angiogenesis via angiocrine role to regulate the STAG1-miR-200a-5p signaling pathway in liver fibrosis.
2023-06-28 | GSE218574 | GEO
Project description: Not available
| S-EPMC1153182 | biostudies-other