{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T06:27:00Z","timestamp":1786602420097,"version":"build-2736575974"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Renal fibrosis is a common pathological outcome of chronic kidney disease and is characterized by persistent profibrotic signaling and impaired cellular homeostasis. Genkwanin (GAK), a natural flavonoid compound, has shown anti-inflammatory and antioxidant activities in several disease models. However, its role in renal fibrosis remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>We investigated the antifibrotic effects of GAK in a TGF-\u03b21\u2013induced HK-2 cell model and a unilateral ureteral obstruction (UUO) mouse model. EMT- and fibrosis-related changes were assessed by RT-qPCR, Western blotting, immunofluorescence, and histological staining. The involvement of TGF-\u03b21\/SMAD2 and \u03b2-catenin signaling was examined using pharmacological modulators. Autophagic flux was evaluated by tandem mCherry-GFP-LC3 analysis, transmission electron microscopy, and autophagy-related protein expression. TFEB inhibition was used to further assess the role of lysosome\u2013autophagy regulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>GAK significantly attenuated TGF-\u03b21\u2013induced EMT and extracellular matrix accumulation in HK-2 cells and reduced renal fibrotic injury in UUO mice. Mechanistically, GAK decreased p-SMAD2 expression and limited \u03b2-catenin nuclear redistribution, indicating suppression of both TGF-\u03b21\/SMAD2 and \u03b2-catenin signaling. In addition, GAK improved autophagic flux and increased TFEB expression. Inhibition of TFEB partially weakened the protective effects of GAK on fibrosis-related and autophagy-related changes, suggesting that TFEB-mediated lysosome\u2013autophagy function contributes to its antifibrotic action.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      In conclusion, GAK alleviates renal fibrosis\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      , at least in part, by suppressing TGF-\u03b21\/SMAD2 and \u03b2-catenin signaling and by restoring TFEB-associated autophagic flux.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1861855","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T05:32:00Z","timestamp":1786599120000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Genkwanin mitigates renal fibrosis by reprogramming profibrotic signaling and restoring TFEB-mediated autophagy"],"prefix":"10.3389","volume":"17","author":[{"given":"Shen","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Urology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Hubei Provincial Clinical Medical Research Center for Minimally Invasive Treatment of Urology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"He","sequence":"additional","affiliation":[{"name":"Department of Urology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Hubei Provincial Clinical Medical Research Center for Minimally Invasive Treatment of Urology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Gan","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Nephrology, First Affiliated Hospital of Kunming Medical University","place":["Kunming, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ZongHai","family":"He","sequence":"additional","affiliation":[{"name":"First Department of Urology, First Affiliated Hospital of Kunming Medical University","place":["Kunming, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2757","DOI":"10.2147\/ijgm.s524138","article-title":"The dual role and therapeutic implications of the Wnt\/\u03b2-Catenin pathway in diabetic kidney disease","volume":"18","author":"Adeerjiang","year":"2025","journal-title":"Int. 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