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It was aimed to study the protective effect of SFRP5 against RF and interference with Wnt\/\u03b2\u2010catenin signaling pathway for the first time. First, the therapeutic efficacy of SFRP5 was evaluated by adenovirus overexpression in rats with unilateral ureteral obstruction (UUO) <jats:italic>in vivo<\/jats:italic>. Thirty-six rats were randomly divided into the sham, UUO, and SFRP5 (UUO + Ad-SFRP5) groups. Half rats in each group were selected at random for euthanasia at 7 days and the others until 14 days. Then, the transforming growth factor (TGF)-\u03b21-induced epithelial\u2013mesenchymal transition (EMT) was established in HK-2 cells <jats:italic>in vitro<\/jats:italic>. The cells were divided into four groups: the control group, the TGF-\u03b21 group, the TGF-\u03b21 + SFRP5 group, and the TGF-\u03b21 + SFRP5 + anti-SFRP5 group. The makers of EMT and Wnt\/\u03b2\u2010catenin pathway proteins were investigated. In the UUO model, expression of SFRP5 showed compensatory upregulation, and adenoviral-mediated SFRP5 over-expression remarkably attenuated RF, as demonstrated by maintenance of E-cadherin and suppression of \u03b1-smooth muscle actin (SMA). <jats:italic>In vitro<\/jats:italic>, SFRP5 was shown to inhibit TGF-\u03b21-mediated positive regulation of \u03b1-SMA, fibronectin, collagen I but negative regulation of E-cadherin. Furthermore, SFRP5 abrogated activation of Wnt\/\u03b2-catenin, which was the essential pathway in EMT and RF pathogenesis. The changes after a neutralizing antibody to SFRP5 confirmed the specificity of SFRP5 for inhibition. These findings suggest that SFRP5 can directly ameliorate EMT and protect against RF by inhibiting Wnt\/\u03b2-catenin pathway.<\/jats:p>","DOI":"10.1515\/med-2024-0934","type":"journal-article","created":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T16:41:45Z","timestamp":1711644105000},"source":"Crossref","is-referenced-by-count":3,"title":["Secreted frizzled-related protein 5 protects against renal fibrosis by inhibiting Wnt\/\u03b2-catenin pathway"],"prefix":"10.1515","volume":"19","author":[{"given":"Dai","family":"Deng","sequence":"first","affiliation":[{"name":"Department of Nephrology, Beijing Friendship Hospital, Capital Medical University , 100050 , Beijing , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongli","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Beijing Friendship Hospital, Capital Medical University , 100050 , Beijing , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yahui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Emergency, China Rehabilitation Research Center , Beijing , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Beijing Friendship Hospital, Capital Medical University , 100050 , Beijing , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zongli","family":"Diao","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Beijing Friendship Hospital, Capital Medical University , 100050 , Beijing , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenhu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Beijing Friendship Hospital, Capital Medical University , 95 Yong\u2019an Road, Xicheng District, 100050 , Beijing , China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2024,3,28]]},"reference":[{"key":"2024060509334226178_j_med-2024-0934_ref_001","unstructured":"GBD chronic kidney disease collaboration. 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Targeting the Wnt\/\u03b2-catenin signaling pathway as a potential therapeutic strategy in renal tubulointerstitial fibrosis. Front Pharmacol. 2021;12:719880. 10.3389\/fphar.2021.719880.","DOI":"10.3389\/fphar.2021.719880"},{"key":"2024060509334226178_j_med-2024-0934_ref_005","doi-asserted-by":"crossref","unstructured":"Zhang J, Li Y, Zhang X, Tian Z, Liu C, Wang S, et al. Cellular senescence of renal tubular epithelial cells in renal fibrosis. Front Endocrinol (Lausanne). 2023;141085605. 10.3389\/fendo.2023.1085605.","DOI":"10.3389\/fendo.2023.1085605"},{"key":"2024060509334226178_j_med-2024-0934_ref_006","doi-asserted-by":"crossref","unstructured":"Janda CY, Dang LT, You C, Chang J, Lau W, Zhong ZA, et al. Surrogate Wnt agonists that phenocopy canonical Wnt and \u03b2-catenin signalling. 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