{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T19:38:08Z","timestamp":1789414688816,"version":"build-2803163510"},"reference-count":29,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biology International"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Renal fibrosis driven by TGF\u2010\u03b2\/Smad3 signaling is a critical factor in the advancement of chronic kidney disease, and partial epithelial\u2010to\u2010mesenchymal transition (EMT) in tubular cells plays a significant role in this process. In this study, we explored the reno\u2010protective role of biochanin A (BCA), a natural isoflavone, in mice with unilateral ureter obstruction (UUO) and in cultured renal tubular TCMK1 cells stimulated with the profibrotic cytokine TGF\u2010\u03b21. Our results demonstrated that BCA (20 and 50\u2009mg\/kg) dose\u2010dependently ameliorated structural damage in UUO kidneys with reduced extracellular matrix deposition and downregulated levels of fibrotic genes\n                    <jats:italic>Col1a1<\/jats:italic>\n                    ,\n                    <jats:italic>fibronectin<\/jats:italic>\n                    , and\n                    <jats:italic>\u03b1\u2010SMA<\/jats:italic>\n                    .\n                    <jats:italic>In vitro<\/jats:italic>\n                    , BCA (5 and 10\u2009\u03bcg\/mL) also exhibited a dose\u2010dependent anti\u2010fibrosis effect in TCMK1 cells induced by TGF\u2010\u03b21. Moreover, BCA prevented tubular partial EMT by mitigating the upregulation of mesenchymal marker genes\n                    <jats:italic>N\u2010cadherin<\/jats:italic>\n                    and\n                    <jats:italic>vimentin<\/jats:italic>\n                    in UUO kidneys and TGF\u2010\u03b21\u2010induced TCMK1 cells. BCA treatment also reversed the reduced staining of\n                    <jats:italic>Lotus Tetragonolobus<\/jats:italic>\n                    Lectin and peanut agglutinin, two markers of mature renal tubular epithelia, in UUO kidneys. Mechanistically, BCA inhibited Smad2 and Smad3 phosphorylation and specifically downregulated Smad3 protein expression, without affecting Smad2, in TGF\u2010\u03b21\u2010stimulated TCMK1 cells. Most importantly, in TGF\u2010\u03b21\u2010treated TCMK1 cells, Smad3 overexpression abolished the anti\u2010fibrosis and anti\u2010EMT effects of BCA. In conclusion, our findings demonstrate the potential of BCA as a therapeutic agent against renal fibrosis by inhibiting TGF\u2010\u03b2\/Smad3 signaling\u2010mediated tubular partial EMT.\n                  <\/jats:p>","DOI":"10.1002\/cbin.70098","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T14:58:26Z","timestamp":1761663506000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Biochanin A Attenuates Renal Fibrosis Via Selective Inhibition of Smad3\u2010mediated Epithelial\u2010Mesenchymal Transition in a Murine Unilateral Ureteral Obstruction Model"],"prefix":"10.1002","volume":"50","author":[{"given":"Huai\u2010Ying","family":"Guo","sequence":"first","affiliation":[{"name":"College of Integrated Chinese and Western Medicine and the Affiliated Traditional Chinese Medicine Hospital Southwest Medical University Luzhou China"},{"name":"The Clinical Laboratory, the Affiliated Traditional Chinese Medicine Hospital Southwest Medical University Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Qing","family":"Li","sequence":"additional","affiliation":[{"name":"College of Integrated Chinese and Western Medicine and the Affiliated Traditional Chinese Medicine Hospital Southwest Medical University Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Wei","sequence":"additional","affiliation":[{"name":"The Clinical Laboratory, the Affiliated Traditional Chinese Medicine Hospital Southwest Medical University Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi\u2010Yong","family":"Li","sequence":"additional","affiliation":[{"name":"The Clinical Laboratory, the Affiliated Traditional Chinese Medicine Hospital Southwest Medical University Luzhou 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