{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T17:49:46Z","timestamp":1793555386566,"version":"4.5.0"},"reference-count":35,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"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":["82030021"],"award-info":[{"award-number":["82030021"]}],"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":["82430022"],"award-info":[{"award-number":["82430022"]}],"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":["82200678"],"award-info":[{"award-number":["82200678"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background &amp; Aims<\/jats:title>\n                    <jats:p>Transforming growth factor (TGF)\u2010\u03b2 signalling plays an indispensable role in promoting the activation of hepatic stellate cells and inducing epithelial\u2010mesenchymal transition of hepatocytes during liver fibrosis. Liver sinusoidal endothelial cells (LSECs) undergo capillarisation and promote inflammatory responses following liver injury. Here, we investigated the role of TGF\u2010\u03b2 signalling in LSECs during liver fibrosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Single\u2010cell RNA\u2010sequencing (scRNA\u2010seq) datasets from healthy individuals and patients with cirrhosis were analysed to evaluate the expression of TGF\u2010\u03b2 signalling related genes. Endothelial cell\u2010specific\n                      <jats:italic>Tgfbr2<\/jats:italic>\n                      \u2010knockout mice were generated and experimental liver fibrosis was induced by carbon tetrachloride injection or choline\u2010deficient high\u2010fat diet. Liver fibrosis was evaluated by qPCR, western blotting, histology and immunostaining. Primary LSECs were isolated and gene expression was analysed by RNA sequencing. Hepatic inflammation was assessed by qPCR, immunostaining and flow cytometry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      ScRNA\u2010seq analysis based on GSE136103 showed\n                      <jats:italic>TGFBR2<\/jats:italic>\n                      is elevated in LSECs from cirrhotic patients compared to healthy controls. LSEC\u2010specific\n                      <jats:italic>Tgfbr2<\/jats:italic>\n                      depletion ameliorated injury\u2010induced LSEC capillarisation and endothelial\u2010to\u2010mesenchymal transition. RNA sequencing revealed that\n                      <jats:italic>Tgfbr2<\/jats:italic>\n                      deficiency downregulated chemokine expression and reshaped angiocrine signalling in LSECs. Endothelial\u2010specific\n                      <jats:italic>Tgfbr2<\/jats:italic>\n                      deletion inhibited pro\u2010inflammatory monocyte recruitment and attenuated hepatic inflammation during liver fibrosis. Furthermore,\n                      <jats:italic>Tgfbr2<\/jats:italic>\n                      deletion in LSECs inhibited macrophage chemotaxis in\u00a0vitro.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Endothelial TGF\u2010\u03b2 signalling aggravates injury\u2010induced liver fibrosis by promoting LSECs capillarisation, EndMT and proinflammatory monocyte recruitment. These findings show the potential of targeting\n                      <jats:italic>TGFBR2<\/jats:italic>\n                      in LSECs to control liver fibrotic diseases.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70227","type":"journal-article","created":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T11:52:58Z","timestamp":1754049178000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Endothelial\n                    <i>Tgfbr2<\/i>\n                    Deficiency Ameliorate Liver Fibrosis Through Regulating Angiocrine Signalling and Macrophage Accumulation"],"prefix":"10.1111","volume":"45","author":[{"given":"Ru","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Changzheng Hospital, Naval Medical University  Shanghai China"},{"name":"Department of Gastroenterology Shanghai East Hospital, Tongji University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1713-4854","authenticated-orcid":false,"given":"Juan","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai East Hospital, Tongji University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke\u2010Qi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Changzheng Hospital, Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang\u2010Peng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Changzheng Hospital, Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen\u2010Hong","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai East Hospital, Tongji University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Changzheng Hospital, Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5712-6614","authenticated-orcid":false,"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Changzheng Hospital, Naval Medical University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7137-112X","authenticated-orcid":false,"given":"Wei\u2010Fen","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Changzheng Hospital, Naval Medical University  Shanghai China"},{"name":"Department of Gastroenterology Shanghai East Hospital, Tongji University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(22)00047-X"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2018.09.002"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm-20-4354"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.07.009"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-020-00411-3"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22351"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00428.2016"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.12.017"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.08.033"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI143690"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-019-0102-3"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a021873"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.119.314813"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/1751-2980.13161"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-022-01569-x"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2019.11.010"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/iep.12008"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114396"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3317"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.671081"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202003721"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2024.05.014"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31617"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.06.043"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.6A0114-004RR"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.812431"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2022.110289"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2018.07.008"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01169-0"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-2101-4"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29834"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.03.013"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10061248"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.12.025"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.02.026"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.70227","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T14:06:21Z","timestamp":1764597981000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.70227"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":35,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1111\/liv.70227"],"URL":"https:\/\/doi.org\/10.1111\/liv.70227","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8]]},"assertion":[{"value":"2025-01-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70227"}}