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Kidney fibrosis is driven by multiple profibrotic factors. This project examined the regulatory function of WNT1\u2010inducible\u2010signaling pathway protein 1 (WISP1) in the development of kidney fibrosis. Induction of WISP1 by transforming growth factor beta 1 (TGF\u2010\u03b21), and the role of WISP1 in TGF\u2010\u03b21\/Smad signaling and fibrotic responses, was examined in multiple kidney cells. Kidney expression of WISP1 was examined in mouse models of unilateral ureter obstruction (UUO) and streptozotocin\u2010induced diabetic nephropathy. WISP1 antibody was administered to UUO mice during the induction of kidney injury and the impact on kidney fibrosis was examined. WISP1 expression was upregulated in both mouse models. TGF\u2010\u03b21\u2010induced expression of WISP1 and profibrotic genes in cultured kidney cells via TGF\u2010\u03b2R1. Recombinant WISP1\u2010induced expression of TGF\u2010\u03b2R1 in kidney cells. Suppression of WISP1 by shRNA or neutralizing antibody reduced TGF\u2010\u03b21\u2010mediated activation of Smad3, fibrotic gene expression, and fibroblast proliferation. Treatment with WISP1 antibody inhibited the development of kidney fibrosis in UUO mice. WISP1 mediates the profibrotic effects of TGF\u2010\u03b21 in kidney cells and in kidney disease. Pharmacological blockade of WISP1 exhibits potential as a novel therapy for inhibiting kidney fibrosis.<\/jats:p>","DOI":"10.1096\/fj.202000953r","type":"journal-article","created":{"date-parts":[[2020,9,9]],"date-time":"2020-09-09T03:48:01Z","timestamp":1599623281000},"page":"14507-14520","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["WNT1\u2010inducible\u2010signaling pathway protein 1 regulates the development of kidney fibrosis through the TGF\u2010\u03b21 pathway"],"prefix":"10.1096","volume":"34","author":[{"given":"Bo","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Kidney Transplantation Nephropathy Hospital The First Affiliated Hospital of Xi'an Jiaotong University Xi'an P.R. 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