{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T01:52:29Z","timestamp":1779328349052,"version":"3.51.4"},"reference-count":26,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T00:00:00Z","timestamp":1728259200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T00:00:00Z","timestamp":1728259200000},"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":["82360131"],"award-info":[{"award-number":["82360131"]}],"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":["81960120"],"award-info":[{"award-number":["81960120"]}],"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":["81660110"],"award-info":[{"award-number":["81660110"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004479","name":"Natural Science Foundation of Jiangxi Province","doi-asserted-by":"publisher","award":["20224BAB216021"],"award-info":[{"award-number":["20224BAB216021"]}],"id":[{"id":"10.13039\/501100004479","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2024,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Liver fibrosis is characterized by a wound\u2010healing response and may progress to liver cirrhosis and even hepatocellular carcinoma. Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) is a tumor suppressor that participates in malignant diseases. However, the role of LHPP in liver fibrosis has not been determined. Herein, the function and regulatory network of LHPP were explored in liver fibrosis. The expression of LHPP in human and murine fibrotic liver tissues was assessed via immunohistochemistry and Western blot analysis. In addition, liver fibrosis was induced in wild\u2010type (WT) and LHPP\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    (KO) mice after carbon tetrachloride (CCl\n                    <jats:sub>4<\/jats:sub>\n                    ) or thioacetamide (TAA) treatment. The effect of LHPP was systematically assessed by using specimens acquired from the above murine models. The functional role of LHPP was further explored by detecting the pathway activity of TGF\u2010\u03b2\/Smad3 and apoptosis after interfering with LHPP in\u00a0vitro. To explore whether the function of LHPP depended on the TGF\u2010\u03b2\/Smad3 pathway in\u00a0vivo, an inhibitor of the TGF\u2010\u03b2\/Smad3 pathway was used in CCl\n                    <jats:sub>4<\/jats:sub>\n                    \u2010induced WT and KO mice. LHPP expression was downregulated in liver tissue samples from fibrosis patients and fibrotic mice. LHPP deficiency aggravated CCl\n                    <jats:sub>4<\/jats:sub>\n                    \u2010 and TAA\u2010induced liver fibrosis. Moreover, through immunoblot analysis, we identified the TGF\u2010\u03b2\/Smad3 pathway as a key downstream pathway of LHPP in\u00a0vivo and in\u00a0vitro. The effect of LHPP deficiency was reversed by inhibiting the TGF\u2010\u03b2\/Smad3 pathway in liver fibrosis. These results revealed that LHPP deficiency exacerbates liver fibrosis through the TGF\u2010\u03b2\/Smad3 pathway. LHPP may be a potential therapeutic target in hepatic fibrosis.\n                  <\/jats:p>","DOI":"10.1096\/fj.202400117rr","type":"journal-article","created":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T10:58:27Z","timestamp":1728298707000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["LHPP deficiency aggravates liver fibrosis through TGF\u2010\u03b2\/Smad3 signaling"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1514-2303","authenticated-orcid":false,"given":"Yue","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University  Nanchang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7099-0343","authenticated-orcid":false,"given":"Bi\u2010min","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University  Nanchang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8438-6718","authenticated-orcid":false,"given":"Wang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The Second Affiliated Hospital, Hengyang Medical School, University of South China  Hengyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2215-214X","authenticated-orcid":false,"given":"Peng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University  Nanchang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5691-486X","authenticated-orcid":false,"given":"Linxiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University  Nanchang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7367-2359","authenticated-orcid":false,"given":"Yuan","family":"Nie","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University  Nanchang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3755-5133","authenticated-orcid":false,"given":"Chenkai","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University  Nanchang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8854-831X","authenticated-orcid":false,"given":"Xuan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University  Nanchang 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