{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T16:17:04Z","timestamp":1774973824638,"version":"3.50.1"},"reference-count":43,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T00:00:00Z","timestamp":1730937600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T00:00:00Z","timestamp":1730937600000},"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":["31171087"],"award-info":[{"award-number":["31171087"]}],"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":["30970662"],"award-info":[{"award-number":["30970662"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aim<\/jats:title>\n                    <jats:p>Hepatic fibrosis is a common outcome of chronic liver injury and can eventually lead to cirrhosis, which is a major public health concern. Hepatic stellate cells (HSCs) are the major producers of extracellular matrix (ECM) and regulate the synthesis and decomposition of ECM, but the specific mechanism of them remains unclear. Transient receptor potential channel 6 (TRPC6), a non\u2010selective cation channel, plays an important role in organic fibrosis. However, the role of TRPC6 in liver fibrosis is rarely studied.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Here, we investigated the function of TRPC6 in the activation of the human hepatic stellate cell line LX\u20102 in vitro and bile duct ligation (BDL)\u2010induced hepatic fibrosis in vivo by western blot, Ca\n                      <jats:sup>2+<\/jats:sup>\n                      imaging, and immunohistochemistry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We first found that TRPC6 was upregulated in fibrotic liver tissues and TRPC6 knockout inhibited BDL\u2010induced hepatic fibrosis. Transforming growth factor\u2010\u03b21 (TGF\u2010\u03b21) treatment increased TRPC6 expression and thapsigargin (Tg)\u2010mediated SOCE in LX\u20102 cells, which was decreased by the TRPC6 specific inhibitor SAR7334. Blockage of TRPC6 by SAR7334 or TRPC6\u2010shRNA transfection attenuated TGF\u2010\u03b21\u2010induced LX\u20102 cell activation and proliferation via the PI3K\/AKT\/p70S6K signaling pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These observations suggested that TRPC6 contribute to LX\u20102 cell activation and hepatic fibrosis, and downregulation of TRPC6 may become a therapeutic strategy for the treatment of hepatic fibrosis in the future.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jgh.16802","type":"journal-article","created":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T02:40:03Z","timestamp":1731033603000},"page":"294-303","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Transient receptor potential channel 6 knockout ameliorates hepatic fibrosis by inhibiting the activation and proliferation of hepatic stellate cells"],"prefix":"10.1111","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0114-5936","authenticated-orcid":false,"given":"Xixi","family":"Zeng","sequence":"first","affiliation":[{"name":"Department of Pathology Renmin Hospital of Wuhan University  Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanhong","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Anatomy Tongji Medical College of Huazhong University of Science and Technology  Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiyi","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pain Union Hospital, Tongji Medical College of Huazhong University of Science and Technology  Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,11,7]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.4.2247"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/4136253"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000011518"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0752-1"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30193"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.04.011"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2018.07.045"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2006.08.050"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0712288105"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-05161-1_14"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9010126"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.01785"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000000295"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2016.12.002"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2012.08.017"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2016.09.039"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-017-4470-9"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-1052-5"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.13278"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2016.63"},{"key":"e_1_2_6_22_1","first-page":"7211","article-title":"CD133 mediates the TGF\u2010\u03b21\u2010induced activation of the PI3K\/ERK\/P70S6K signaling pathway in gastric cancer cells","volume":"14","author":"Zhu Y","year":"2017","journal-title":"Oncol. Lett."},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00471.2012"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.mcg.0000155516.02468.0f"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1203013"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b20-00903"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40779-023-00494-4"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjms.2023.08.016"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-2596-8"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.1316"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-06043-0"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2023-329671"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2023.0506"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1089\/rej.2018.2104"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1080\/17435390.2019.1661041"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2015.03.001"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2016-0090OC"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.12638"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2015.08.010"},{"key":"e_1_2_6_40_1","first-page":"81","article-title":"Antifibrotic effects of tanshinol in experimental hepatic fibrosis by targeting PI3K\/AKT\/mTOR\/p70S6K1 signaling pathways","volume":"23","author":"Peng R","year":"2017","journal-title":"Discov. Med."},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2013.08.009"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2014.08.006"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2017.12.007"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.26469"}],"container-title":["Journal of Gastroenterology and Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jgh.16802","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jgh.16802","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jgh.16802","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T01:14:45Z","timestamp":1771204485000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jgh.16802"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,7]]},"references-count":43,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1111\/jgh.16802"],"URL":"https:\/\/doi.org\/10.1111\/jgh.16802","archive":["Portico"],"relation":{},"ISSN":["0815-9319","1440-1746"],"issn-type":[{"value":"0815-9319","type":"print"},{"value":"1440-1746","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,7]]},"assertion":[{"value":"2024-08-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}