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Our prior studies demonstrated that SHBG can attenuate MASLD by limiting hepatic lipid deposition, partly through suppression of lipogenic pathways, in both cellular and animal models. In the present work, we have examined whether SHBG could protect against development of liver fibrosis. For this purpose, in vitro and in vivo studies were performed. In vitro, we used co-cultures of human hepatocellular carcinoma cell line (HepG2) and human hepatic stellate cell line (LX-2) cells transfected using an SHBG expression vector vs. vehicle and treated with transforming growth factor beta 1 (TGF-\u03b21). For in vivo studies we used wild-type and human SHBG transgenic mice developing liver fibrosis induced by carbon tetrachloride (CCl4). Our results clearly showed that SHBG overexpression reduced the TGF-\u03b21-induced expression in collagen in LX-2 cells. Moreover, SHBG overexpression reduced the CCl4 induced liver fibrosis in both male and female mice. Histological examination revealed that SHBG transgenic mice had reduced NAS score and decreased collagen accumulation, assessed by Sirious Red staining. In addition, human SHBG transgenic mice treated with CCl4 exhibited lower collagen 1A1 (Col1A1) protein levels when compared with wild-type CCl4 treated mice. Mechanistically, SHBG attenuated fibrosis primarily through modulation of the TGF-\u03b21\/matrix metalloproteinases (MMPs)\/tissue inhibitor metalloproteinases 1 (TIMP1) axis, characterized by reduced TGF-\u03b21 levels, increased metalloprotease activity, and decreased TIMP1 levels compared with wild-type CCl4 treated mice. Notably, female SHBG transgenic mice exhibited greater protection against fibrosis than males, indicating a sex-dependent effect likely mediated by differences in sex steroid signaling. Taken together, we demonstrate for the first time that SHBG protects against liver fibrosis by promoting collagen degradation via the TGF-\u03b21\/MMPs\/TIMP1 pathway. Further research is needed to elucidate the role of sex steroids in the regulation of MMPs and the observed sexual dimorphism.<\/jats:p>","DOI":"10.3390\/ijms27114893","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T12:45:08Z","timestamp":1780404308000},"page":"4893","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Sex Hormone-Binding Globulin Prevents Carbon Tetrachloride-Induced Liver Fibrosis Development"],"prefix":"10.3390","volume":"27","author":[{"given":"Anna","family":"\u00c1lvarez-Guaita","sequence":"first","affiliation":[{"name":"Diabetes and Metabolism Research Unit, Vall d\u2019Hebron Research Institute (VHIR), Vall d\u2019Hebron University Hospital, 08035 Barcelona, Spain"},{"name":"Autonomous University of Barcelona, 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Brians\u00f3-Llort","sequence":"additional","affiliation":[{"name":"Diabetes and Metabolism Research Unit, Vall d\u2019Hebron Research Institute (VHIR), Vall d\u2019Hebron University Hospital, 08035 Barcelona, Spain"},{"name":"Autonomous University of Barcelona, 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Cabrera-Serra","sequence":"additional","affiliation":[{"name":"Diabetes and Metabolism Research Unit, Vall d\u2019Hebron Research Institute (VHIR), Vall d\u2019Hebron University Hospital, 08035 Barcelona, Spain"},{"name":"Autonomous University of Barcelona, 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidia","family":"Fuertes-Rioja","sequence":"additional","affiliation":[{"name":"Diabetes and Metabolism Research Unit, Vall d\u2019Hebron Research Institute (VHIR), Vall d\u2019Hebron University Hospital, 08035 Barcelona, Spain"},{"name":"Autonomous University of Barcelona, 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Ramos-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Diabetes and Metabolism Research Unit, Vall d\u2019Hebron Research Institute (VHIR), Vall d\u2019Hebron University Hospital, 08035 Barcelona, Spain"},{"name":"Autonomous University of Barcelona, 08193 Barcelona, Spain"},{"name":"Diabetes and Metabolism Research Unit and CIBERDEM, Vall d\u2019Hebron Research Institute (VHIR), 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Teresa","family":"Salcedo-Allende","sequence":"additional","affiliation":[{"name":"Human Pathology Department, Vall d\u2019Hebron University Hospital, 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3109-1721","authenticated-orcid":false,"given":"Cristina","family":"Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Diabetes and Metabolism Research Unit, Vall d\u2019Hebron Research Institute (VHIR), Vall d\u2019Hebron University Hospital, 08035 Barcelona, Spain"},{"name":"Autonomous University of Barcelona, 08193 Barcelona, Spain"},{"name":"Diabetes and Metabolism Research Unit and CIBERDEM, Vall d\u2019Hebron Research Institute (VHIR), 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0475-3096","authenticated-orcid":false,"given":"Rafael","family":"Sim\u00f3","sequence":"additional","affiliation":[{"name":"Diabetes and Metabolism Research Unit, Vall d\u2019Hebron Research Institute (VHIR), Vall d\u2019Hebron University Hospital, 08035 Barcelona, Spain"},{"name":"Autonomous University of Barcelona, 08193 Barcelona, Spain"},{"name":"Diabetes and Metabolism Research Unit and CIBERDEM, Vall d\u2019Hebron Research Institute (VHIR), 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Selva","sequence":"additional","affiliation":[{"name":"Diabetes and Metabolism Research Unit, Vall d\u2019Hebron Research Institute (VHIR), Vall d\u2019Hebron University Hospital, 08035 Barcelona, Spain"},{"name":"Autonomous University of Barcelona, 08193 Barcelona, Spain"},{"name":"Diabetes and Metabolism Research Unit and CIBERDEM, Vall d\u2019Hebron Research Institute (VHIR), 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"R13","DOI":"10.1530\/JOE-16-0070","article-title":"Plasma steroid-binding proteins: Primary gatekeepers of steroid hormone action","volume":"230","author":"Hammond","year":"2016","journal-title":"J. Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Siiteri, P.K., Murai, J.T., Raymoure, W.J., Kuhn, R.W., Hammond, G.L., and Nisker, J.A. (1982). The serum transport of steroid hormones. Proceedings of the 1981 Laurentian Hormone Conference, Elsevier.","DOI":"10.1016\/B978-0-12-571138-8.50016-0"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1056\/NEJMoa0804381","article-title":"Sex hormone-binding globulin and risk of type 2 diabetes in women and men","volume":"361","author":"Ding","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1097\/XCE.0000000000000057","article-title":"Relevance of low testosterone to nonalcoholic fatty liver disease","volume":"4","author":"Mody","year":"2015","journal-title":"Cardiovasc. Endocrinol."},{"key":"ref_5","first-page":"545","article-title":"Sex hormone-binding globulin reduction in metabolic disorders may play a role in NAFLD development","volume":"158","author":"Hernandez","year":"2017","journal-title":"Endocrinology"},{"key":"ref_6","first-page":"3979","article-title":"Monosaccharide-induced lipogenesis regulates the human hepatic sex hormone-binding globulin gene","volume":"117","author":"Selva","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s43162-023-00220-5","article-title":"Sex hormone-binding globulin (SHBG) as a predictor of liver fibrosis in subjects with nonalcoholic fatty liver disease (NAFLD)","volume":"35","author":"Hesham","year":"2023","journal-title":"Egypt. J. Intern. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3598","DOI":"10.1002\/jcp.30818","article-title":"Transforming growth factor-beta 1: A new factor reducing hepatic SHBG production in liver fibrosis","volume":"237","author":"Hernandez","year":"2022","journal-title":"J. Cell. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"372","DOI":"10.2337\/db11-0727","article-title":"Potential role of tumor necrosis factor-\u03b1 in downregulating sex hormone-binding globulin","volume":"61","author":"Lecube","year":"2012","journal-title":"Diabetes"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1210\/me.2011-1321","article-title":"Molecular mechanism of TNF\u03b1-induced down-regulation of SHBG expression","volume":"26","author":"Lecube","year":"2012","journal-title":"Mol. Endocrinol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1210\/me.2012-1152","article-title":"IL1\u03b2 down-regulation of sex hormone-binding globulin production by decreasing HNF-4\u03b1 via MEK-1\/2 and JNK MAPK pathways","volume":"26","author":"Hernandez","year":"2012","journal-title":"Mol. Endocrinol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1172\/JCI24282","article-title":"Liver fibrosis","volume":"115","author":"Bataller","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1111\/febs.13665","article-title":"TGF-\u03b2 signalling and liver disease","volume":"283","author":"Fabregat","year":"2016","journal-title":"FEBS J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e20190103","DOI":"10.1084\/jem.20190103","article-title":"Transforming growth factor-\u03b2 in tissue fibrosis","volume":"217","author":"Frangogiannis","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Chow, L.N., Schreiner, P., Ng, B.Y.Y., Lo, B., Hughes, M.R., Scott, R.W., Gusti, V., Lecour, S., Simonson, E., and Manisali, I. (2016). Impact of a CXCL12\/CXCR4 antagonist in bleomycin (BLM)-induced pulmonary fibrosis and carbon tetrachloride (CCl4)-induced hepatic fibrosis in mice. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0151765"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"109","DOI":"10.3181\/0707-MR-190","article-title":"Mechanisms of fibrogenesis","volume":"233","author":"Kisseleva","year":"2008","journal-title":"Exp. Biol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1172\/JCI30542","article-title":"Models of liver fibrosis: Exploring the dynamic nature of inflammation and repair in a solid organ","volume":"117","author":"Iredale","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1177\/0023677215571192","article-title":"The carbon tetrachloride model in mice","volume":"49","author":"Scholten","year":"2015","journal-title":"Lab. Anim."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Niu, L., Cui, X., Qi, Y., Xie, D., Wu, Q., Chen, X., Ge, J., and Liu, Z. (2016). Involvement of TGF-\u03b21\/Smad3 signaling in carbon tetrachloride-induced acute liver injury in mice. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0156090"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1016\/j.jhep.2007.02.003","article-title":"Expression of MMPs and TIMPs in liver fibrosis\u2014A systematic review with special emphasis on anti-fibrotic strategies","volume":"46","author":"Hemmann","year":"2007","journal-title":"J. Hepatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/S0168-8278(97)80359-5","article-title":"TIMP expression in toxic and cholestatic liver injury in rat","volume":"27","author":"Roeb","year":"1997","journal-title":"J. Hepatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"100870","DOI":"10.1016\/j.jhepr.2023.100870","article-title":"Sex differences in chronic liver disease and benign liver lesions","volume":"5","author":"Cooper","year":"2023","journal-title":"JHEP Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.jceh.2017.09.004","article-title":"Matrix metalloproteinases (MMPs) in liver diseases","volume":"7","author":"Naim","year":"2017","journal-title":"J. Clin. Exp. Hepatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1152\/physrev.00013.2007","article-title":"Hepatic stellate cells: Protean, multifunctional, and enigmatic cells of the liver","volume":"88","author":"Friedman","year":"2008","journal-title":"Physiol. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Gupta, P., Sata, T.N., Yadav, A.K., Mishra, A., Vats, N., Hossain, M., Sanal, M.G., and Venugopal, S.K. (2019). TGF-\u03b2 induces liver fibrosis via miRNA-181a-mediated downregulation of augmenter of liver regeneration in hepatic stellate cells. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0214534"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1080\/713611034","article-title":"Hepatotoxicity and mechanism of action of carbon tetrachloride as a toxicological model","volume":"33","author":"Weber","year":"2003","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.trsl.2020.03.008","article-title":"Sex-related differences in the pathogenesis of organ fibrosis","volume":"222","author":"Gonzalez","year":"2020","journal-title":"Transl. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1016\/j.cgh.2014.12.033","article-title":"Association between endogenous sex hormones and liver fat in a multiethnic study of atherosclerosis","volume":"13","author":"Lazo","year":"2015","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.diabres.2011.07.029","article-title":"Serum sex hormone-binding globulin levels are independently associated with nonalcoholic fatty liver disease in people with type 2 diabetes","volume":"94","author":"Shin","year":"2011","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.2337\/db23-0982","article-title":"Association between low sex hormone-binding globulin and increased risk of type 2 diabetes is mediated by increased visceral and liver fat: Results from observational and Mendelian randomization analyses","volume":"73","author":"Stangl","year":"2024","journal-title":"Diabetes"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1210\/jc.2018-00740","article-title":"Sex hormone-binding globulin expression correlates with acetyl-coenzyme A carboxylase and triglyceride content in human liver","volume":"104","author":"Hernandez","year":"2019","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"382","DOI":"10.5604\/01.3001.0009.8593","article-title":"Testosterone, sex hormone-binding globulin and nonalcoholic fatty liver disease: A systematic review and meta-analysis","volume":"16","author":"Jaruvongvanich","year":"2017","journal-title":"Ann. Hepatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.bpg.2011.02.011","article-title":"Anti-fibrogenic strategies and the regression of fibrosis","volume":"25","author":"Kisseleva","year":"2011","journal-title":"Best Pract. Res. Clin. Gastroenterol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.3748\/wjg.v10.i9.1315","article-title":"Suppressive effects of 17\u03b2-estradiol on hepatic fibrosis in CCl4-induced rat model","volume":"10","author":"Liu","year":"2004","journal-title":"World J. Gastroenterol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"250","DOI":"10.3748\/wjg.v10.i2.250","article-title":"Effects of estradiol on liver estrogen receptor-alpha and its mRNA expression in hepatic fibrosis in rats","volume":"10","author":"Xu","year":"2004","journal-title":"World J. Gastroenterol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1002\/hep.510290307","article-title":"Suppressive effects of estradiol on dimethylnitrosamine-induced fibrosis of the liver in rats","volume":"29","author":"Yasuda","year":"1999","journal-title":"Hepatology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"883","DOI":"10.3748\/wjg.v8.i5.883","article-title":"Estrogen reduces CCl4-induced liver fibrosis in rats","volume":"8","author":"Xu","year":"2002","journal-title":"World J. Gastroenterol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1007\/s00109-025-02569-2","article-title":"Sex hormone-binding globulin restrains hepatic fibrosis via inhibition of Tgf\u03b2 expression","volume":"103","author":"Lee","year":"2025","journal-title":"J. Mol. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1210\/mend.12.1.0050","article-title":"Human sex hormone-binding globulin gene expression in transgenic mice","volume":"12","author":"Deol","year":"1998","journal-title":"Mol. Endocrinol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1002\/hep.20701","article-title":"Design and validation of a histological scoring system for nonalcoholic fatty liver disease","volume":"41","author":"Kleiner","year":"2005","journal-title":"Hepatology"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/11\/4893\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T04:11:08Z","timestamp":1780632668000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/11\/4893"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,28]]},"references-count":40,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ijms27114893"],"URL":"https:\/\/doi.org\/10.3390\/ijms27114893","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,28]]}}}