{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T07:58:16Z","timestamp":1790582296286,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012543","name":"Youth Science Foundation of Guangxi Medical University","doi-asserted-by":"publisher","award":["GXMUYSF202348"],"award-info":[{"award-number":["GXMUYSF202348"]}],"id":[{"id":"10.13039\/501100012543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biochemistry &amp;amp; Function"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Hepatic stellate cell (HSC) activation is a key mediator in hepatic fibrosis, with glycolysis serving a key regulatory function. S100 calcium\u2010binding protein 16 (S100A16) has been associated with various pathologies; however, its function and underlying mechanisms in liver fibrosis remains elusive. This study aimed to elucidate the functional role of S100A16 in HSC activation and its interaction with Erb\u2010B2 receptor tyrosine kinase 2 (ERBB2)\u2010mediated glycolysis. Transforming growth factor\u2010\u03b21 (TGF\u2010\u03b21)\u2010stimulated human liver stellate cells (LX2) and carbon tetrachloride (CCl\n                    <jats:sub>4<\/jats:sub>\n                    )\u2010induced mice were used as in vitro and in vivo models, respectively. Cell proliferation and alpha\u2010smooth muscle actin (\u03b1\u2010SMA) expression were detected by Cell Counting Kit\u20108 (CCK\u20108) assay and immunofluorescence. Glycolysis was detected via measuring the extracellular acidification rate (ECAR), lactate production, glucose uptake, and glycolytic enzyme levels. Molecular interactions were analyzed through bioinformatics and co\u2010immunoprecipitation. Liver injury and fibrosis were assessed using hematoxylin and eosin (H&amp;E)\/Masson staining. Expression of S100A16, ERBB2, and fibrosis markers were quantified using quantitative real\u2010time PCR (qRT\u2010PCR) and Western blot. S100A16 was upregulated in fibrotic liver tissues and TGF\u2010\u03b21\u2010stimulated LX2 cells. TGF\u2010\u03b21 increased lactate production and glycolysis, whereas S100A16 knockdown produced the opposite effects. Additionally, TGF\u2010\u03b21 enhanced cell proliferation and upregulated \u03b1\u2010SMA, Collagen 1, and Fibronectin levels, but these effects were attenuated by either S100A16 knockdown or glycolysis inhibition. S100A16 interacted with ERBB2 and promoted its expression. ERBB2 knockdown reduced TGF\u2010\u03b21\u2010induced glycolysis and HSC activation, along with reduced cell proliferation, effects that were inhibited by S100A16 overexpression. Furthermore, S100A16 knockdown ameliorated CCl\n                    <jats:sub>4<\/jats:sub>\n                    \u2010induced liver injury and fibrosis, decreased serum lactate levels, and reduced S100A16 and ERBB2 expression, thereby suppressing glycolysis. Collectively, S100A16 promotes HSC activation and liver fibrosis through ERBB2\u2010mediated glycolysis, highlighting the S100A16\u2010ERBB2\u2010glycolysis axis as a potential therapeutic target.\n                  <\/jats:p>","DOI":"10.1002\/cbf.70299","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T14:45:12Z","timestamp":1788792312000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["S100 Calcium\u2010Binding Protein 16 (S100A16) Promotes Hepatic Stellate Cell Activation Via Erb\u2010B2 Receptor Tyrosine Kinase 2 (ERBB2)\u2010mediated Glycolysis to Facilitate Liver Fibrosis"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3161-7594","authenticated-orcid":false,"given":"Shiyu","family":"Ou","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Liuzhou Workers' Hospital (The Fourth Affiliated Hospital of Guangxi Medical University) Liuzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Guangxi Zhuang Autonomous Region Brain Hospital Liuzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Liuzhou Workers' Hospital (The Fourth Affiliated Hospital of Guangxi Medical University) Liuzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Liuzhou Workers' Hospital (The Fourth Affiliated Hospital of Guangxi Medical University) Liuzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijiang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Liuzhou Workers' Hospital (The Fourth Affiliated Hospital of Guangxi Medical University) Liuzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuwen","family":"Weng","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Liuzhou Workers' Hospital (The Fourth Affiliated Hospital of Guangxi Medical University) Liuzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinping","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Liuzhou Workers' Hospital (The Fourth Affiliated Hospital of Guangxi Medical University) Liuzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingheng","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Liuzhou Workers' Hospital (The Fourth Affiliated Hospital of Guangxi Medical University) Liuzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0648-6767","authenticated-orcid":false,"given":"Ling","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Liuzhou Workers' Hospital (The Fourth Affiliated Hospital of Guangxi Medical University) Liuzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0501-9231","authenticated-orcid":false,"given":"Zhongzhuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Liuzhou Workers' Hospital (The Fourth Affiliated Hospital of Guangxi Medical University) Liuzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-020-00372-7"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-024-01084-2"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-022-03041-5"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2023.06.013"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-021-00658-9"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-024-00867-y"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2024.149958"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2024.122498"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aohep.2025.101896"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2023.07.035"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.5114\/ceji.2024.145013"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgg.2022.02.013"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10565-024-09929-7"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.2147\/CMAR.S508047"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.73365"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-04249-8"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2022.155271"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00894-021-04986-9"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-73574-7"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-021-01641-4"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-92687-1"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202415007"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2023.115497"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2024.01.012"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq1039"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt1115"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2023.117516"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000569"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.03.008"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom13071070"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000001133"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2023.04.011"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-022-03837-2"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aohep.2022.100700"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2024.155465"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13402-022-00683-8"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-05293-6"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2024.13376"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2016.4627"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-022-01904-8"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2019.04.012"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-023-08310-x"}],"container-title":["Cell Biochemistry and Function"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbf.70299","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cbf.70299","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbf.70299","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T07:45:03Z","timestamp":1790581503000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/cbf.70299"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":42,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/cbf.70299"],"URL":"https:\/\/doi.org\/10.1002\/cbf.70299","archive":["Portico"],"relation":{},"ISSN":["0263-6484","1099-0844"],"issn-type":[{"value":"0263-6484","type":"print"},{"value":"1099-0844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"2026-03-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70299"}}