{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:56:05Z","timestamp":1760061365922,"version":"build-2065373602"},"reference-count":32,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,6,25]],"date-time":"2018-06-25T00:00:00Z","timestamp":1529884800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81401348","91442119"],"award-info":[{"award-number":["81401348","91442119"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biochemistry &amp;amp; Function"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:sec><jats:label\/><jats:p>Dysfunctional autophagy in intrahepatic biliary epithelial cells (IBECs) is the main mechanism underlying the pathogenesis of bile duct lesions in primary biliary cholangitis. Autophagy may be a key pathogenesis for aetiology of primary biliary cholangitis. Immunoblotting and immunofluorescence analyses were used for the evaluation of autophagy in human intrahepatic biliary epithelial cells (HiBECs) at various time points. Glycochenodeoxycholate (GCDC) induced autophagy in HiBECs; the ratio of microtubule\u2010associated protein light chain 3\u2010II\/microtubule\u2010associated protein light chain 3\u2010I (LC3\u2010II\/LC3\u2010I) expression markedly increased at 48\u00a0hours, and then declined. However, compared with cells treated with GCDC alone, the expression of LC3\u2010II increased and the clearance of autophagosome enhanced in GCDC\u2010treated cells cocultured with mesenchymal stem cells (MSCs). Furthermore, the level of phosphorylation of signal transducer and activator of transcription 3 (pSTAT3) decreased in HiBECs cocultured with MSCs relative to those cultured without MSCs. Following STAT3 silencing, decreased expression of phosphorylated eukaryotic initiation factor 2\u03b1 was consistently observed. The present data suggest that mesenchymal stem cells may enhance autophagic flux of HiBECs through the inhibition of STAT3 activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance paragraph<\/jats:title><jats:p>The present findings constitute the first report that human umbilical cord\u2010derived MSCs enhance autophagic flux in HiBECs through a STAT3\u2010dependent way:\n<jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>MSCs enhance the autophagic flux by increasing the formation of autophagosome and autolysosome in GCDC\u2010treated HiBECs.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>MSCs decrease the STAT3 activity and the expression of eIF2\u03b1 in GCDC\u2010treated HiBECs; in addition, MSCs increase the expression of PKR.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>With STAT3 silencing, MSCs enhance neither the levels of LC3II nor the expression of PKR in GCDC\u2010treated HiBECs.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/cbf.3340","type":"journal-article","created":{"date-parts":[[2018,7,4]],"date-time":"2018-07-04T23:15:52Z","timestamp":1530746152000},"page":"280-287","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Mesenchymal stem cells enhance autophagy of human intrahepatic biliary epithelial cells in vitro"],"prefix":"10.1002","volume":"36","author":[{"given":"Yun","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology Drum Tower Clinical Medical College of Nanjing Medical University  Nanjing Jiangsu China"},{"name":"Department of Rheumatology and Immunology The Affiliated Drum Tower Hospital of Nanjing University Medical School  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department 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