Dataset Information

Proteomic analysis of septic renal acute phase response

ABSTRACT: Sepsis-induced acute kidney injury (AKI) is the most common form of AKI with poor outcomes. Renal proteomic analysis after bacterial lipopolysaccharide (LPS) administration revealed that the local renal acute phase reaction (APR) is one of the strongest responses of the kidney during septic AKI in mice. Evaluation of mRNA expression confirmed that most acute phase proteins were produced in the kidney. Our study also provides missing information on the time course of septic renal APR. Proteomic analysis of LPS-induced AKI demonstrated a marked upregulation of local renal acute phase response (APR) that commenced a few hours post injection and peaked at 24 h. Much more APPs were involved in the renal APR than previously identified.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Clostridioides difficile 630 Pseudomonas aeruginosa PAO1 Entamoeba histolytica HM-1:IMSS-A Entamoeba histolytica Geobacter sulfurreducens Beta vulgaris subsp. vulgaris Helicobacter pylori 26695 Ovis aries Dentex dentex Chlorocebus sabaeus Ensifer adhaerens Thermoplasma acidophilum DSM 1728 Pyrococcus furiosus Schizosaccharomyces pombe 927 Medicago truncatula Pectobacterium carotovorum Taeniopygia guttata Sus scrofa domesticus Bos taurus Equus caballus Candida albicans SC5314 Physcomitrium patens Bursaphelenchus xylophilus Bacillus subtilis subsp. subtilis NCIB 3610 = ATCC 6051 = DSM 10 Synechocystis sp. PCC 6803 Emiliania huxleyi Drosophila Callinectes sapidus Dasypogon diadema Trypanosoma cruzi Bacillus subtilis subsp. subtilis str. 168 Ophrys x arachnitiformis subsp. archipelagi Schizosaccharomyces pombe Enterococcus faecalis Trypanosoma brucei brucei Pseudomonas syringae Oncorhynchus mykiss Candida albicans Helianthus annuus Cyanophora paradoxa Mycolicibacterium smegmatis Populus yunnanensis Trypanosoma brucei Paucilactobacillus suebicus Mus musculus Ctenopharyngodon idella Caenorhabditis elegans Danio rerio Crithidia fasciculata Ophrys sphegodes Solanum lycopersicum Lingula anatina Ophrys garganica Bradyrhizobium diazoefficiens USDA 110 Escherichia coli Acidithiobacillus ferrooxidans ATCC 53993 Nephila clavipes Chlamydomonas reinhardtii Apostichopus japonicus Triticum aestivum Craterostigmus tasmanianus Listeria monocytogenes Allexis Ostreococcus tauri Camelus dromedarius Vitis vinifera Saccharomyces cerevisiae Parasynechococcus marenigrum WH 8102 Zea mays Macaca mulatta Histomonas meleagridis Botrytis cinerea Human immunodeficiency virus 1 Macaca fascicularis Ictalurid herpesvirus 1 Acinetobacter baumannii Cercopithecidae Staphylococcus sp. 1 Drosophila melanogaster Oryza sativa Indica Group Bovine leukemia virus Rattus norvegicus Heloderma suspectum suspectum Homo sapiens subsp. 'Denisova' Sphingomonas sp. Leaf257 Gallus gallus Cavia porcellus Pseudomonas fluorescens SBW25 Sinorhizobium meliloti BL225C Lotus japonicus Scolopendra morsitans Rhizobium sp. Leaf68 Lithobius forficatus Bombyx mori Scutigera coleoptrata Pseudomonas putida KT2440 Streptococcus dysgalactiae subsp. equisimilis SK1249 Rattus rattus Bradyrhizobium japonicum Strigamia maritima Staphylococcus aureus Aerococcus urinae NBRC 15544 = CCUG 36881 Citrobacter rodentium Alteromonadales Canis lupus familiaris Vitis riparia Flavobacterium columnare Globicatella sanguinis Mycobacterium tuberculosis albimanus section Pyricularia oryzae Streptococcus agalactiae FSL S3-026 Arabidopsis thaliana Pseudomonas pseudoalcaligenes CECT 5344 Pseudomonas putida BIRD-1 Schizosaccharomyces pombe 972h- Homo sapiens

TISSUE(S): Kidney

SUBMITTER: Marko Fonovic

LAB HEAD: Marko Fonovic

PROVIDER: PXD014664 | Pride | 2020-01-08

REPOSITORIES: Pride

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Publications

The Acute Phase Response Is a Prominent Renal Proteome Change in Sepsis in Mice.

Róka Beáta B Tod Pál P Kaucsár Tamás T Vizovišek Matej M Vidmar Robert R Turk Boris B Fonović Marko M Szénási Gábor G Hamar Péter P

International journal of molecular sciences 20191227 1

(1) Background: Sepsis-induced acute kidney injury (AKI) is the most common form of acute kidney injury (AKI). We studied the temporal profile of the sepsis-induced renal proteome changes. (2) Methods: Male mice were injected intraperitoneally with bacterial lipopolysaccharide (LPS) or saline (control). Renal proteome was studied by LC-MS/MS (ProteomeXchange: PXD014664) at the early phase (EP, 1.5 and 6 h after 40 mg/kg LPS) and the late phase (LP, 24 and 48 h after 10 mg/kg LPS) of LPS-induced ...[more]

PMID: 31892161

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Project description:Background: Septic acute kidney injury (AKI) causes high mortality in critical care units, and no effective therapy exists in clinical treatment. In the current study, water and ethanol extracts of Hydrangea paniculata (HP), a traditional Chinese medicinal plant, were used to test its renoprotective effects in a lipopolysaccharide (LPS)-induced murine model of septic AKI. Methods: C57BL/6 mice were orally pretreated with HP three times, and then intraperitoneal LPS injection was used to induce septic AKI. Blood from animals was collected for biochemical analysis and kidneys were obtained for pathological analysis. Kidney tissue homogenates were used to investigate the effect of HP on inflammation and oxidative stress. Immunohistochemistry was used to investigate tubular cell apoptosis. Flow cytometry was conducted to analyze leukocyte infiltration into the kidneys. Blood cell counts were used to analyze changes in peripheral leukocytes. In vitro studies with Ana1 and HK-2 cells stimulated by LPS were used to investigate the anti-inflammatory effects and inhibition of signaling pathways by HP. Results: HP significantly decreased blood urea nitrogen and plasma neutrophil gelatinase-associated lipocalin concentrations, as well as tubulointerstitium injuries in septic AKI mice. Moreover, HP administration improved animal survival following lethal LPS injections. HP ameliorated apoptosis of tubular cells by inhibiting the cleavage of caspase 3 and caspase 7. HP also showed pronounced antioxidant activity in AKI kidneys. HP showed anti-inflammatory effects by inhibiting the infiltration of neutrophils and macrophages into kidney tissues induced by LPS, as well as inhibiting the production of cytokines and chemokines. Possible molecular mechanisms included HP inhibition of NF-?B nuclear translocation in LPS-induced macrophages and tubular cells, and reduction of STAT3, STAT1, and ERK1/2 phosphorylation stimulated by LPS in vitro. Single acute toxicity tests confirmed that HP, even at 5 g/kg dosage, does not cause animal death. Pharmacokinetics also showed that coumarins from HP could be metabolized into two bioactive compounds, umbelliferone, and esculetin. Conclusions: HP extract may protect renal function in LPS-induced AKI by anti-inflammatory and antioxidant activities, and has potential in the critical care of AKI.

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