{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T08:57:09Z","timestamp":1768035429041,"version":"3.49.0"},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,12,4]],"date-time":"2022-12-04T00:00:00Z","timestamp":1670112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004479","name":"Natural Science Foundation of Jiangxi Province","doi-asserted-by":"publisher","award":["20202BAB206011"],"award-info":[{"award-number":["20202BAB206011"]}],"id":[{"id":"10.13039\/501100004479","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cholestasis is a main clinical feature of biliary atresia (BA), which leads to liver fibrosis (LF). The focus of BA treatment is preventing and slowing the progress of LF. This study reports the improvement effect of anlotinib on common bile duct ligature (BDL)\u2010induced LF in young rats. The BDL young rats were treated with anlotinib and the serum levels of aspartate aminotransferase, alanine aminotransferase, albumin, and total bilirubin were determined. Histological staining was performed and pathological changes in liver tissue were observed. The expression levels of \u03b1\u2010SMA, collagen I, CD31, TGF\u2010\u03b21, phospho\u2010VEGFR2, phospho\u20104E\/BP1, and phospho\u2010S6K1 were determined. The results showed that anlotinib significantly improved the liver function and histopathological injury of BDL rats, inhibited the deposition of collagen and hepatocyte apoptosis, and downregulated the protein expression of \u03b1\u2010SMA and collagen I. Furthermore, anlotinib treatment significantly inhibited microvascular formation in the liver and downregulated the expression level of phospho\u2010VEGFR2, thereby suggesting that the antifibrosis effect of anlotinib may be achieved by antiangiogenesis. In addition, anlotinib downregulated the expression of phospho\u2010S6K1 and upregulated the expression of phospho\u20104E\/BP1, two downstream proteins of the mammalian target of rapamycin (mTOR) pathway. MHY1485, an agonist of mTOR, significantly reversed the inhibitory effect of anlotinib on angiogenesis and LF\u00a0but did not influence the effect of anlotinib on the downregulation of phospho\u2010VEGFR2 expression. Together, the above\u2010mentioned results suggest that the effect of anlotinib on BDL\u2010induced LF involves at least antiangiogenesis regulated by the VEGFR2\/mTOR signaling pathway.<\/jats:p>","DOI":"10.1002\/ddr.22019","type":"journal-article","created":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T00:37:20Z","timestamp":1670200640000},"page":"143-155","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Anlotinib improves bile duct ligature\u2010induced liver fibrosis in rats via antiangiogenesis regulated by VEGFR2\/mTOR pathway"],"prefix":"10.1002","volume":"84","author":[{"given":"Jun","family":"Lei","sequence":"first","affiliation":[{"name":"Department of General Surgery Jiangxi Provincial Children's Hospital Nanchang Jiangxi P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Li","sequence":"additional","affiliation":[{"name":"Rehabilitation Center Jiangxi Provincial Children's Hospital Nanchang Jiangxi P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongyan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pathology Jiangxi Provincial Children's Hospital Nanchang Jiangxi P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of General Surgery Jiangxi Provincial Children's Hospital Nanchang Jiangxi P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiwen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of neonatal surgery Jiangxi Provincial Children's Hospital Nanchang Jiangxi P.R. 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