Neder, Thomas H. and Schrankl, Julia and Fuchs, Michaela A. A. and Broeker, Katharina A. E. and Wagner, Charlotte (2021) Endothelin receptors in renal interstitial cells do not contribute to the development of fibrosis during experimental kidney disease. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 473 (10). pp. 1667-1683. ISSN 0031-6768, 1432-2013
Full text not available from this repository. (Request a copy)Abstract
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 (ETAETBflfl)-E-flfl FoxD1(Cre+) 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | THICK ASCENDING LIMB; ANGIOTENSIN-II; MESSENGER-RNA; ETB-RECEPTOR; INJURY; MECHANISMS; INHIBITION; EXPRESSION; GROWTH; MICE; Endothelin-1; Endothelin receptors; Kidney fibrosis; Unilateral ureter occlusion; Adenine-induced nephropathy |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Armin Kurtz |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 28 Jul 2022 07:55 |
| Last Modified: | 28 Jul 2022 07:55 |
| URI: | https://pred.uni-regensburg.de/id/eprint/46014 |
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