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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 ET<jats:sub>A<\/jats:sub>-receptor (ET<jats:sub>A<\/jats:sub>-R) gene expression in interstitial and mesangial cells, while the gene expression of ET<jats:sub>B<\/jats:sub>-receptor (ET<jats:sub>B<\/jats:sub>-R) did not change. Conditional deletion of ET<jats:sub>A<\/jats:sub>-R and ET<jats:sub>B<\/jats:sub>-R gene expression in the FoxD1 stromal cell compartment which includes interstitial cells significantly reduced renal ET<jats:sub>A<\/jats:sub>-R gene expression and moderately lowered renal ET<jats:sub>B<\/jats:sub>-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 ET<jats:sub>A<\/jats:sub><jats:sup>flfl<\/jats:sup>ET<jats:sub>B<\/jats:sub><jats:sup>flfl<\/jats:sup> FoxD1<jats:sup>Cre+<\/jats:sup> mice (ET-Ko). In summary, our findings suggest that adenine feeding and UUO activate endothelin signaling in interstitial cells which is due to upregulated ET<jats:sub>A<\/jats:sub>-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.<\/jats:p>","DOI":"10.1007\/s00424-021-02604-4","type":"journal-article","created":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T23:12:39Z","timestamp":1628205159000},"page":"1667-1683","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Endothelin receptors in renal interstitial cells do not contribute to the development of fibrosis during experimental kidney disease"],"prefix":"10.1007","volume":"473","author":[{"given":"Thomas H.","family":"Neder","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Schrankl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michaela A. 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