{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:11:28Z","timestamp":1786115488061,"version":"build-2736575974"},"reference-count":31,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:00:00Z","timestamp":1775174400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:00:00Z","timestamp":1775174400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82570725"],"award-info":[{"award-number":["82570725"]}],"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":["81700550"],"award-info":[{"award-number":["81700550"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["20ZR1411200"],"award-info":[{"award-number":["20ZR1411200"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["22140900700"],"award-info":[{"award-number":["22140900700"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["23ZR1411300"],"award-info":[{"award-number":["23ZR1411300"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["24YF2704400"],"award-info":[{"award-number":["24YF2704400"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Liver fibrosis represents a critical pathological stage in chronic liver disease, characterized by excessive activation of hepatic stellate cells (\n                    <jats:styled-content style=\"fixed-case\">HSCs<\/jats:styled-content>\n                    ) and dysregulated immune cell recruitment. Our previous studies demonstrated that overexpressing tyrosine kinase receptor B (\n                    <jats:styled-content style=\"fixed-case\">TrkB<\/jats:styled-content>\n                    ) in\n                    <jats:styled-content style=\"fixed-case\">HSCs<\/jats:styled-content>\n                    inhibits their activation, thereby alleviating liver fibrosis. However, its functional significance in hepatocytes\u2014the predominant parenchymal cells orchestrating liver homeostasis\u2014remains poorly understood. Here, we investigate the mechanistic interplay between hepatocyte\u2010specific\n                    <jats:styled-content style=\"fixed-case\">TrkB<\/jats:styled-content>\n                    signalling and liver fibrosis progression. Through integrated in\u00a0vivo animal models and in\u00a0vitro two\u2010 and three\u2010dimensional systems, we demonstrate that elevated\n                    <jats:styled-content style=\"fixed-case\">TrkB<\/jats:styled-content>\n                    expression in hepatocytes reduces pro\u2010fibrotic and inflammatory cytokines, attenuates\n                    <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>\n                    activation via paracrine signalling, and impairs monocyte\u2010derived macrophage (\n                    <jats:styled-content style=\"fixed-case\">MoMF<\/jats:styled-content>\n                    ) recruitment. Mechanistically,\n                    <jats:styled-content style=\"fixed-case\">TrkB<\/jats:styled-content>\n                    modulates the\n                    <jats:styled-content style=\"fixed-case\">TGF\u03b2<\/jats:styled-content>\n                    \/\n                    <jats:styled-content style=\"fixed-case\">SMAD3<\/jats:styled-content>\n                    pathway by inhibiting p\u2010\n                    <jats:styled-content style=\"fixed-case\">SMAD3<\/jats:styled-content>\n                    nuclear translocation, thus suppressing\n                    <jats:styled-content style=\"fixed-case\">FOS<\/jats:styled-content>\n                    transcription. As a core component of the\n                    <jats:styled-content style=\"fixed-case\">AP<\/jats:styled-content>\n                    \u20101 transcription factor complex,\n                    <jats:styled-content style=\"fixed-case\">FOS<\/jats:styled-content>\n                    directly regulates\n                    <jats:styled-content style=\"fixed-case\">CCL2<\/jats:styled-content>\n                    , a pivotal chemokine for macrophage recruitment. Collectively, these results establish\n                    <jats:styled-content style=\"fixed-case\">TrkB<\/jats:styled-content>\n                    as a key regulatory node in the\n                    <jats:styled-content style=\"fixed-case\">TGF\u03b2<\/jats:styled-content>\n                    \/\n                    <jats:styled-content style=\"fixed-case\">SMAD3<\/jats:styled-content>\n                    \/\n                    <jats:styled-content style=\"fixed-case\">FOS<\/jats:styled-content>\n                    \/\n                    <jats:styled-content style=\"fixed-case\">CCL2<\/jats:styled-content>\n                    signalling cascade, orchestrating macrophage\u2010mediated fibrotic responses in the liver.\n                  <\/jats:p>","DOI":"10.1111\/cpr.70202","type":"journal-article","created":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T03:45:00Z","timestamp":1775274300000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hepatocyte\n                    <scp>TrkB<\/scp>\n                    Acts as a Gatekeeper Against\n                    <scp>MASH<\/scp>\n                    \u2010Related Liver Fibrosis by Suppressing the\n                    <scp>TGF\u03b2<\/scp>\n                    \/\n                    <scp>CCL2<\/scp>\n                    Axis and Macrophage Infiltration"],"prefix":"10.1111","volume":"59","author":[{"given":"Yueying","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology Zhongshan Hospital, Fudan University  Shanghai China"},{"name":"Shanghai Institute of Liver Diseases  Shanghai China"},{"name":"Department of Oncology Renji Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Zhongshan Hospital, Fudan University  Shanghai China"},{"name":"Shanghai Institute of Liver Diseases  Shanghai China"},{"name":"Department of Gastroenterology Huadong Hospital, Shanghai Medical College, Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuxuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Zhongshan Hospital, Fudan University  Shanghai China"},{"name":"Shanghai Institute of Liver Diseases  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kefan","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Zhongshan Hospital, Fudan University  Shanghai China"},{"name":"Shanghai Institute of Liver Diseases  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9124-8238","authenticated-orcid":false,"given":"Heming","family":"Wang","sequence":"additional","affiliation":[{"name":"Joint Laboratory of Biomaterials and Translational Medicine, Puheng Biomedicine Co., Ltd  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1691-323X","authenticated-orcid":false,"given":"Yicheng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Chinese Medicine Guangdong Laboratory\/State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuqiang","family":"Weng","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Zhongshan Hospital, Fudan University  Shanghai China"},{"name":"Shanghai Institute of Liver Diseases  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xizhong","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Zhongshan Hospital, Fudan University  Shanghai China"},{"name":"Shanghai Institute of Liver Diseases  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangqi","family":"Song","sequence":"additional","affiliation":[{"name":"Joint Laboratory of Biomaterials and Translational Medicine, Puheng Biomedicine Co., Ltd  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4922-0659","authenticated-orcid":false,"given":"Changfeng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Zhongshan Hospital, Fudan University  Shanghai China"},{"name":"Shanghai Institute of Liver Diseases  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qunyan","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Zhongshan Hospital, Fudan University  Shanghai China"},{"name":"Shanghai Institute of Liver Diseases  Shanghai China"},{"name":"Department of Gastroenterology and Hepatology Zhongshan Hospital (Xiamen), Fudan University  Xiamen China"},{"name":"Shanghai Geriatric Medical Center  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5995-7673","authenticated-orcid":false,"given":"Ling","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Zhongshan Hospital, Fudan University  Shanghai China"},{"name":"Shanghai Institute of Liver Diseases  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.09.014"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-020-00372-7"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-051116-052415"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-023-00807-x"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.15715"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2022.05.056"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.07.014"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.162270"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.2174\/187152708783885174"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1336"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1073"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2017.09.005"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000319"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30921"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2021.113888"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2020.06.026"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2020.06.015"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1586\/17474124.2015.1073106"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.ado9880"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/29814"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a022137"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-023-00759-2"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.2.12b.1687"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2418"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.19.9.2078"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abm3436"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201902055R"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2022.175420"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2023.113694"},{"key":"e_1_2_11_31_1","first-page":"1133","article-title":"The Regulatory Role of the BDNF\/TrkB Pathway in Organ and Tissue Fibrosis","volume":"36","author":"Hang P.\u2010Z.","year":"2021","journal-title":"Histology and Histopathology"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-017-1298-1"}],"container-title":["Cell Proliferation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cpr.70202","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cpr.70202","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cpr.70202","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T03:17:52Z","timestamp":1785986272000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cpr.70202"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,3]]},"references-count":31,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1111\/cpr.70202"],"URL":"https:\/\/doi.org\/10.1111\/cpr.70202","archive":["Portico"],"relation":{},"ISSN":["0960-7722","1365-2184"],"issn-type":[{"value":"0960-7722","type":"print"},{"value":"1365-2184","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,3]]},"assertion":[{"value":"2026-01-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70202"}}