{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T10:59:26Z","timestamp":1788260366231,"version":"build-2803163510"},"reference-count":48,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,9,11]],"date-time":"2019-09-11T00:00:00Z","timestamp":1568160000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81560566"],"award-info":[{"award-number":["81560566"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81570558"],"award-info":[{"award-number":["81570558"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Liver fibrosis (LF) is the result of a vicious cycle between inflammation\u2010induced chronic hepatocyte injury and persistent activation of hepatic stellate cells (HSCs). Mesenchymal stem cell (MSC)\u2010based therapy may represent a potential remedy for treatment of LF. However, the fate of transplanted MSCs in LF remains largely unknown. In the present study, the fate and antifibrotic effect of MSCs were explored in a LF model induced by CCl<jats:sub>4<\/jats:sub> in mouse. Additionally, MSCs were stimulated in vitro with LF\u2010associated factors, tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1), interferon\u2010\u03b3 (IFN\u2010\u03b3), and transforming growth factor\u2010\u03b21 (TGF\u2010\u03b21), to mimic the LF microenvironment. We unveiled that MSCs exhibited autophagy in response to the LF microenvironment through <jats:italic>Becn1<\/jats:italic> upregulation both in vivo and in vitro. However, autophagy suppression induced by <jats:italic>Becn1<\/jats:italic> knockdown in MSCs resulted in enhanced antifibrotic effects on LF. The improved antifibrotic potential of MSCs may be attributable to their inhibitory effects on T lymphocyte infiltration, HSCs proliferation, as well as production of TNF\u2010\u03b1, IFN\u2010\u03b3, and TGF\u2010\u03b21, which may be partially mediated by elevated paracrine secretion of PTGS2\/PGE<jats:sub>2<\/jats:sub>. Thus, autophagy manipulation in MSCs may be a novel strategy to promote their antifibrotic efficacy.<\/jats:p>","DOI":"10.1002\/jcp.29176","type":"journal-article","created":{"date-parts":[[2019,9,11]],"date-time":"2019-09-11T10:00:04Z","timestamp":1568196004000},"page":"2722-2737","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Autophagy inhibition via <i>Becn1<\/i> downregulation improves the mesenchymal stem cells antifibrotic potential in experimental liver fibrosis"],"prefix":"10.1002","volume":"235","author":[{"given":"Hang Yu","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory of Xingjiang Phytomedicine Resources and Utilization, Ministry of Education, School of Pharmacy Shihezi University  Shihezi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5746-6368","authenticated-orcid":false,"given":"Can","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology and Pathophysiology Chengdu Medical College  Chengdu China"},{"name":"Sichuan Clinical Research Center for Geriatrics The First Affiliated Hospital of Chengdu Medical College  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei Hua","family":"Liu","sequence":"additional","affiliation":[{"name":"Sichuan Clinical Research Center for Geriatrics The First Affiliated Hospital of Chengdu Medical College  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng Mei","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Pathology and Pathophysiology Chengdu Medical College  Chengdu China"},{"name":"Sichuan Clinical Research Center for Geriatrics The First Affiliated Hospital of Chengdu Medical College  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Surgery The First Affiliated Hospital of Chengdu Medical College  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li Na","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pathology and Pathophysiology Chengdu Medical College  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"De Hua","family":"Kong","sequence":"additional","affiliation":[{"name":"Sichuan Clinical Research Center for Geriatrics The First Affiliated Hospital of Chengdu Medical College  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang An","family":"Hu","sequence":"additional","affiliation":[{"name":"Sichuan Clinical Research Center for Geriatrics The First Affiliated Hospital of Chengdu Medical College  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Liu","sequence":"additional","affiliation":[{"name":"Sichuan Clinical Research Center for Geriatrics The First Affiliated Hospital of Chengdu Medical College  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Wu","sequence":"additional","affiliation":[{"name":"Deep\u2010Underground Medicine Laboratory West China Hospital of Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pathology and Pathophysiology Chengdu Medical College  Chengdu China"},{"name":"Sichuan Clinical Research Center for Geriatrics The First Affiliated Hospital of Chengdu Medical College  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi Lun","family":"Liu","sequence":"additional","affiliation":[{"name":"Sichuan Clinical Research Center for Geriatrics The First Affiliated Hospital of Chengdu Medical College  Chengdu China"},{"name":"Department of Surgery The First Affiliated Hospital of Chengdu Medical College  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,9,11]]},"reference":[{"key":"e_1_2_10_1_2_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1999.5851"},{"key":"e_1_2_10_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.01.030"},{"key":"e_1_2_10_1_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2016.09.008"},{"key":"e_1_2_10_1_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3109"},{"key":"e_1_2_10_1_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2017.08.030"},{"key":"e_1_2_10_1_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.100"},{"key":"e_1_2_10_1_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s\u201041577\u2010018\u20100095\u20102"},{"key":"e_1_2_10_1_9_1","doi-asserted-by":"publisher","DOI":"10.2217\/rme.15.14"},{"key":"e_1_2_10_1_10_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.28771"},{"key":"e_1_2_10_1_11_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1102108"},{"key":"e_1_2_10_1_12_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013101068"},{"key":"e_1_2_10_1_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M602097200"},{"key":"e_1_2_10_1_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev"},{"key":"e_1_2_10_1_15_1","doi-asserted-by":"publisher","DOI":"10.5966\/sctm.2015\u20100420"},{"key":"e_1_2_10_1_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr"},{"key":"e_1_2_10_1_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.36"},{"key":"e_1_2_10_1_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2014.85"},{"key":"e_1_2_10_1_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010018\u201022857\u2010x"},{"key":"e_1_2_10_1_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1483"},{"key":"e_1_2_10_1_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2015.1110666"},{"key":"e_1_2_10_1_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2014.11.004"},{"key":"e_1_2_10_1_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl\u20102014\u2010306842"},{"key":"e_1_2_10_1_24_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159\u20108290.CD\u201014\u20100049"},{"key":"e_1_2_10_1_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.14299"},{"key":"e_1_2_10_1_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2542"},{"key":"e_1_2_10_1_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12709"},{"key":"e_1_2_10_1_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2016.48"},{"key":"e_1_2_10_1_29_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102010\u201012\u2010324038"},{"key":"e_1_2_10_1_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3516"},{"key":"e_1_2_10_1_31_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27727"},{"key":"e_1_2_10_1_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c120035"},{"key":"e_1_2_10_1_33_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI20039"},{"key":"e_1_2_10_1_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2012.02.005"},{"key":"e_1_2_10_1_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2007.11.014"},{"key":"e_1_2_10_1_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10145"},{"key":"e_1_2_10_1_37_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.20\u20101002021"},{"key":"e_1_2_10_1_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27332"},{"key":"e_1_2_10_1_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2010.44"},{"key":"e_1_2_10_1_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2011.11.004"},{"key":"e_1_2_10_1_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3273"},{"key":"e_1_2_10_1_42_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis\u20102013\u201020414"},{"key":"e_1_2_10_1_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.02.039"},{"key":"e_1_2_10_1_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2017.38"},{"key":"e_1_2_10_1_45_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.CAN\u201010\u20104009"},{"key":"e_1_2_10_1_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3002"},{"key":"e_1_2_10_1_47_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.20\u201019.1569912"},{"key":"e_1_2_10_1_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1412"},{"key":"e_1_2_10_1_49_1","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2018.1482150"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcp.29176","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.29176","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcp.29176","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.29176","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T13:00:40Z","timestamp":1712754040000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.29176"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,11]]},"references-count":48,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,3]]}},"alternative-id":["10.1002\/jcp.29176"],"URL":"https:\/\/doi.org\/10.1002\/jcp.29176","archive":["Portico"],"relation":{},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,11]]},"assertion":[{"value":"2019-04-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-08-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-09-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}