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Transient receptor potential canonical 6 (TRPC6) channel inhibition mitigates tubular injury and renal fibrosis in murine models of unilateral ureteral obstruction (UUO) and 2\u2010month chronic post\u2013ischemia\u2010reperfusion injury (2m post\u2010I\/R). Through integrated analysis of single\u2010cell\u2010RNA\u2010sequencing (scRNA\u2010Seq) data from UUO mice treated with the selective TRPC6 inhibitor SH045, here the renoprotective cell composition and cell type\u2010specific transcriptional programs are defined. We explored translational aspects by conducting an in\u2010depth scRNA\u2010Seq analysis of kidney samples from patients with CKD. These results reveal global transcriptional shifts with a dramatic diversification of inflammatory cells, endothelial cells and fibroblasts. Notably, a distinct subpopulation of novel endothelial cells is delineated, which is termed ECRIN, that regulate inflammatory networks implicating VEGF and GAS signaling pathways. The data also indicates\u00a0that inhibition of TRPC6 channels triggers a\n                    <jats:italic>Prnp<\/jats:italic>\n                    transcription factor regulatory network, which contributes to the alleviation of renal fibrosis. The key findings are supported at the protein level by immunofluorescence and western blot analysis. We observed similar patterns in the chronic 2m postI\/R injury model. These findings provide novel insights into the potential therapeutic benefits of TRPC6 inhibition in CKD.\n                  <\/jats:p>","DOI":"10.1002\/advs.202501175","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T04:24:39Z","timestamp":1750134279000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Single\u2010Cell RNA Sequencing Delineates Renal Anti\u2010Fibrotic Mechanisms Mediated by TRPC6 Inhibition"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3840-9077","authenticated-orcid":false,"given":"Yao","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Geriatrics University Medicine Greifswald  17487 Greifswald Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihuang","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Nephrology Shanghai 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