Endothelin receptors in renal interstitial cells do not contribute to the development of fibrosis during experimental kidney disease
| Autor: | Michaela Fuchs, Julia Schrankl, Katharina A.E. Broeker, Thomas H. Neder, Charlotte Wagner |
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| Rok vydání: | 2021 |
| Předmět: |
medicine.hormone
Stromal cell Physiology Clinical Biochemistry Kidney development Kidney urologic and male genital diseases Endothelins Endothelin-1 Endothelin receptors Kidney fibrosis Unilateral ureter occlusion Adenine-induced nephropathy Mice Fibrosis Physiology (medical) medicine Renal fibrosis Animals 570 Biowissenschaften Biologie RNA Messenger Chemistry Adenine Receptor Endothelin A medicine.disease Receptor Endothelin B Endothelin 1 Up-Regulation medicine.anatomical_structure Gene Expression Regulation cardiovascular system Cancer research Kidney Diseases ddc:570 Endothelin receptor Gene Deletion Ureteral Obstruction |
| Zdroj: | Pflügers Archiv - European Journal of Physiology. 473:1667-1683 |
| ISSN: | 1432-2013 0031-6768 |
| Popis: | Renal interstitial fibrosis is characterized by the development of myofibroblasts, originating from resident renal and immigrating cells. Myofibroblast formation and extracellular matrix production during kidney damage are triggered by various factors. Among these, endothelins have been discussed as potential modulators of renal fibrosis. Utilizing mouse models of adenine nephropathy (AN) and unilateral ureter occlusion (UUO), this study aimed to investigate the contribution of endothelin signaling in stromal mesenchymal resident renal interstitial cells. We found in controls that adenine feeding and UUO caused marked upregulations of endothelin-1 (ET-1) gene expression in endothelial and in tubular cells and a strong upregulation of ETA-receptor (ETA-R) gene expression in interstitial and mesangial cells, while the gene expression of ETB-receptor (ETB-R) did not change. Conditional deletion of ETA-R and ETB-R gene expression in the FoxD1 stromal cell compartment which includes interstitial cells significantly reduced renal ETA-R gene expression and moderately lowered renal ETB-R gene expression. ET receptor (ET-R) deletion exerted no apparent effects on kidney development nor on kidney function. Adenine feeding and UUO led to similar increases in profibrotic and proinflammatory gene expression in control as well as in ETAflflETBflfl FoxD1Cre+ mice (ET-Ko). In summary, our findings suggest that adenine feeding and UUO activate endothelin signaling in interstitial cells which is due to upregulated ETA-R expression and enhanced renal ET-1 production Our data also suggest that the activation of endothelin signaling in interstitial cells has less impact for the development of experimentally induced fibrosis. |
| Databáze: | OpenAIRE |
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