{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T09:02:24Z","timestamp":1789549344569,"version":"build-2803163510"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T00:00:00Z","timestamp":1715558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundamental Research Program of Shanxi Province","award":["20210302124615"],"award-info":[{"award-number":["20210302124615"]}]},{"name":"Research Fund for the Doctor Program of Shanxi Province","award":["SD1913"],"award-info":[{"award-number":["SD1913"]}]},{"DOI":"10.13039\/501100008549","name":"Shanxi Medical University","doi-asserted-by":"publisher","award":["XD1913"],"award-info":[{"award-number":["XD1913"]}],"id":[{"id":"10.13039\/501100008549","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Cholestatic liver disease (CLD) is a severe disease, which can progress to liver cirrhosis, even liver cancer. Hepatic stellate cells (HSCs) activation plays a crucial role in CLD development. Bone mesenchymal stem cells (BMSCs) treatment was demonstrated to be beneficial in liver diseases. However, the therapeutic effect and mechanism of BMSCs on CLD are poorly known. In the present study, we investigated the therapeutic effects and underlying mechanisms of BMSCs transplantation in mouse models of bile duct ligation-induced cholestatic liver fibrosis (CLF). The results revealed that BMSCs significantly improved liver function and reduced the formation of fibrosis after portal vein transplantation. Mechanistically, after coculturing BMSCs and HSCs, we identified that BMSCs alleviated starvation-induced HSCs activation. Further, BMSCs inhibited HSCs activation by decreasing autophagy, and PI3K\/AKT\/mTOR pathway was involved in the regulation. More importantly, ULK1 is identified as the main autophagy-related gene regulated by BMSCs in HSCs autophagy. Overexpression of ULK1 reversed the suppression of HSCs autophagy by BMSCs. Collectively, our results provide a theoretical basis for BMSCs targeting ULK1 to attenuate HSCs autophagy and activation and suggest that BMSCs or ULK1 may be an alternative therapeutic approach\/target for the treatment of CLF.<\/jats:p>","DOI":"10.1093\/stcltm\/szae028","type":"journal-article","created":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T06:26:30Z","timestamp":1715581590000},"page":"648-660","source":"Crossref","is-referenced-by-count":15,"title":["Bone mesenchymal stem cells improve cholestatic liver fibrosis by targeting ULK1 to regulate autophagy through PI3K\/AKT\/mTOR pathway"],"prefix":"10.1093","volume":"13","author":[{"given":"Tingjuan","family":"Huang","sequence":"first","affiliation":[{"name":"Key Laboratory of Birth Defect and Cell Regeneration, Department of Biochemistry and Molecular Biology, Shanxi Medical University , Taiyuan, 030001 Shanxi , China"},{"name":"Key Laboratory of Coal Environmental Pathogenicity and Prevention, Shanxi Medical University 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Prevention, Shanxi Medical University , Taiyuan, 030001 Shanxi , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Nie","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defect and Cell Regeneration, Department of Biochemistry and Molecular Biology, Shanxi Medical University , Taiyuan, 030001 Shanxi , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, The First Hospital of Shanxi Medical University , Taiyuan, 030001 Shanxi , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shulin","family":"Hou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defect and Cell Regeneration, Department of Biochemistry and Molecular Biology, Shanxi Medical University , Taiyuan, 030001 Shanxi , China"},{"name":"Key Laboratory of Coal Environmental Pathogenicity and 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