{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:38:58Z","timestamp":1787312338555,"version":"build-2736575974"},"reference-count":14,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,2,12]],"date-time":"2020-02-12T00:00:00Z","timestamp":1581465600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Renal fibrosis compromises kidney function, and it is a risk factor for chronic kidney disease (CKD). CKD ultimately progresses to end\u2010stage kidney disease that can be cured only by kidney transplantation. Owing to the increasing number of CKD patients, effective treatment strategies are urgently required for renal fibrosis. TGF\u2010\u03b2 is a well\u2010established fibrogenic factor that signals through SMAD2\/3 signaling pathway. It was shown that there is a cross\u2010talk between TGF\u2010\u03b2\/SMAD and WNT\/\u03b2\u2010catenin signaling pathways in renal tubular epithelial cells, and that a WNT\/\u03b2\u2010catenin inhibitor, ICG\u2010001, ameliorates TGF\u2010\u03b21induced renal fibrosis. IC\u20102, a derivative of ICG\u2010001, has been shown to potently induce hepatocyte differentiation of human mesenchymal stem cells by inhibiting WNT\/\u03b2\u2010catenin signaling. In the present study, we examined the effect of ICG\u2010001, IC\u20102, and IC\u20102 derivatives (IC\u20102\u2010506\u20101, IC\u20102\u2010506\u20102, IC\u20102\u2010506\u20103, IC\u20102\u2010Ar\u2010Cl, IC\u20102\u2010OH, IC\u20102\u2010OTBS, and IC\u20102\u2010F) on TGF\u2010\u03b21\u2013induced SMAD activation and fibrogenic response in immortalized human renal tubular epithelial HK\u20102 cells. All these compounds inhibited LiCl\u2010induced WNT\/\u03b2\u2010catenin reporter activation to a similar extent, whereas ICG\u2010001, IC\u20102\u2010OTBS, and IC\u20102\u2010F almost completely suppressed TGF\u2010\u03b21\u2013induced SMAD reporter activation without apparent cytotoxicity. Phosphorylation of SMAD2\/3 by TGF\u2010\u03b21 was more potently inhibited by IC\u20102\u2010OTBS and IC\u20102\u2010F than by ICG\u2010001 and IC\u20102. IC\u20102\u2010F suppressed TGF\u2010\u03b21\u2013induced COL1A1 protein expression, whereas IC\u20102\u2010506\u20101 and IC\u20102\u2010OTBS suppressed TGF\u2010\u03b21\u2013induced epithelial\u2010mesenchymal transition. These results demonstrated that IC\u20102 derivatives suppress the TGF\u2010\u03b21\u2013induced fibrogenic response of tubular epithelial cells and thus could be promising therapeutic agents for the treatment of renal fibrosis.<\/jats:p>","DOI":"10.1111\/1440-1681.13270","type":"journal-article","created":{"date-parts":[[2020,2,3]],"date-time":"2020-02-03T15:05:34Z","timestamp":1580742334000},"page":"940-946","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["WNT\/\u03b2\u2010catenin signal inhibitor IC\u20102\u2013derived small\u2010molecule compounds suppress TGF\u2010\u03b21\u2013induced fibrogenic response of renal epithelial cells by inhibiting SMAD2\/3 signalling"],"prefix":"10.1111","volume":"47","author":[{"given":"Shotaro","family":"Hoi","sequence":"first","affiliation":[{"name":"Division of Molecular and Genetic Medicine Graduate School of Medicine Tottori University Yonago Japan"},{"name":"Division of Medicine and Clinical Science Faculty of Medicine Tottori University Yonago Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2144-8272","authenticated-orcid":false,"given":"Hiroyuki","family":"Tsuchiya","sequence":"additional","affiliation":[{"name":"Division of Molecular and Genetic Medicine Graduate School of Medicine Tottori University Yonago Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Itaba","sequence":"additional","affiliation":[{"name":"Division of Molecular and Genetic Medicine Graduate School of Medicine Tottori University Yonago Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyosuke","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Division of Molecular and Genetic Medicine Graduate School of Medicine Tottori University Yonago 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