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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Alcoholic liver disease (ALD) is a form of hepatic inflammation. ALD is mediated by gut leakiness. This study evaluates the anti-inflammatory effects of ASCs overexpressing interferon-beta (ASC-IFN-\u03b2) on binge alcohol-induced liver injury and intestinal permeability. In vitro, ASCs were transfected with a non-viral vector carrying the human IFN-\u03b2 gene, which promoted hepatocyte growth factor (HGF) secretion in the cells. To assess the potential effects of ASC-IFN-\u03b2, C57BL\/6 mice were treated with three oral doses of binge alcohol and were administered intraperitoneal injections of ASC-IFN-\u03b2. Mice treated with binge alcohol and administered ASC-IFN-\u03b2 showed reduced liver injury and inflammation compared to those administered a control ASC. Analysis of intestinal tissue from ethanol-treated mice administered ASC-IFN-\u03b2 also indicated decreased inflammation. Additionally, fecal albumin, blood endotoxin, and bacterial colony levels were reduced, indicating less gut leakiness in the binge alcohol-exposed mice. Treatment with HGF, but not IFN-\u03b2 or TRAIL, mitigated the ethanol-induced down-regulation of cell death and permeability in Caco-2 cells. These results demonstrate that ASCs transfected with a non-viral vector to induce IFN-\u03b2 overexpression have protective effects against binge alcohol-mediated liver injury and gut leakiness via HGF.<\/jats:p>","DOI":"10.3390\/ijms25158509","type":"journal-article","created":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T18:21:40Z","timestamp":1722882100000},"page":"8509","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["IFN-\u03b2 Overexpressing Adipose-Derived Mesenchymal Stem Cells Mitigate Alcohol-Induced Liver Damage and Gut Permeability"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1904-077X","authenticated-orcid":false,"given":"Soonjae","family":"Hwang","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Lee Gil Ya Cancer and Diabetes Institute, College of Medicine, Gachon University, Incheon 21999, Republic of Korea"},{"name":"Regeneration Medicine Research Center, Wonju College of Medicine, Yonsei University, Wonju 26426, Gangwon-do, Republic of Korea"},{"name":"Cell Therapy and Tissue Engineering Center, Wonju College of Medicine, Yonsei University, Wonju 26426, Gangwon-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5985-6490","authenticated-orcid":false,"given":"Young Woo","family":"Eom","sequence":"additional","affiliation":[{"name":"Regeneration Medicine Research Center, Wonju College of Medicine, Yonsei University, Wonju 26426, Gangwon-do, Republic of Korea"},{"name":"Cell Therapy and Tissue Engineering Center, Wonju College of Medicine, Yonsei University, Wonju 26426, Gangwon-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"given":"Seong Hee","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, Korea University, Seoul 02841, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Soon Koo","family":"Baik","sequence":"additional","affiliation":[{"name":"Regeneration Medicine Research Center, Wonju College of Medicine, Yonsei University, Wonju 26426, Gangwon-do, Republic of Korea"},{"name":"Department of Internal Medicine, Wonju College of Medicine, Yonsei University, Wonju 26426, Gangwon-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2501-2206","authenticated-orcid":false,"given":"Moon Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Regeneration Medicine Research Center, Wonju College of Medicine, Yonsei University, Wonju 26426, Gangwon-do, Republic of Korea"},{"name":"Department of Internal Medicine, Wonju College of Medicine, Yonsei University, Wonju 26426, Gangwon-do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"79","DOI":"10.14309\/ajg.0000000000000442","article-title":"Rising Mortality from Alcohol-Associated Liver Disease in the United States in the 21st Century","volume":"115","author":"Moon","year":"2020","journal-title":"Am. J. Gastroenterol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1782","DOI":"10.1038\/ajg.2010.46","article-title":"Alcoholic liver disease-related mortality in the United States: 1980\u20132003","volume":"105","author":"Paula","year":"2010","journal-title":"Am. J. Gastroenterol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1111\/j.1572-0241.1999.00797.x","article-title":"Leaky gut in alcoholic cirrhosis: A possible mechanism for alcohol-induced liver damage","volume":"94","author":"Keshavarzian","year":"1999","journal-title":"Am. J. Gastroenterol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Liangpunsakul, S., Toh, E., Ross, R.A., Heathers, L.E., Chandler, K., Oshodi, A., McGee, B., Modlik, E., Linton, T., and Mangiacarne, D. (2017). Quantity of alcohol drinking positively correlates with serum levels of endotoxin and markers of monocyte activation. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-04669-7"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.jhep.2018.02.005","article-title":"Apoptosis of enterocytes and nitration of junctional complex proteins promote alcohol-induced gut leakiness and liver injury","volume":"69","author":"Cho","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"101738","DOI":"10.1016\/j.scr.2020.101738","article-title":"Human mesenchymal stem cell therapy for cartilage repair: Review on isolation, expansion, and constructs","volume":"44","author":"Lam","year":"2020","journal-title":"Stem Cell Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1002\/glia.20841","article-title":"Human bone marrow-derived mesenchymal stem cells induce Th2-polarized immune response and promote endogenous repair in animal models of multiple sclerosis","volume":"57","author":"Bai","year":"2009","journal-title":"Glia"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"6646","DOI":"10.7150\/thno.33741","article-title":"Reversal of bleomycin-induced rat pulmonary fibrosis by a xenograft of human umbilical mesenchymal stem cells from Wharton\u2019s jelly","volume":"9","author":"Chu","year":"2019","journal-title":"Theranostics"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1007\/s10787-019-00683-5","article-title":"Human umbilical cord mesenchymal stem cells alleviate inflammatory bowel disease by inhibiting ERK phosphorylation in neutrophils","volume":"28","author":"Wang","year":"2020","journal-title":"Inflammopharmacology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1080\/1061186X.2020.1775842","article-title":"Engineering mesenchymal stem cells: A novel therapeutic approach in breast cancer","volume":"28","author":"Heidari","year":"2020","journal-title":"J. Drug Target."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s12967-020-02234-x","article-title":"Improved therapeutics of modified mesenchymal stem cells: An update","volume":"18","author":"Ocansey","year":"2020","journal-title":"J. Transl. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1159\/000453166","article-title":"Mesenchymal Stem Cells with Enhanced Bcl-2 Expression Promote Liver Recovery in a Rat Model of Hepatic Cirrhosis","volume":"40","author":"Jin","year":"2016","journal-title":"Cell Physiol. Biochem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1186\/s13287-020-01911-4","article-title":"Mesenchymal stem cell-based Smad7 gene therapy for experimental liver cirrhosis","volume":"11","author":"Su","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1038\/s41419-018-1239-9","article-title":"Therapeutic effect of hepatocyte growth factor-overexpressing bone marrow-derived mesenchymal stem cells on CCl4-induced hepatocirrhosis","volume":"9","author":"Zhang","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_15","first-page":"51","article-title":"Viral vector systems for gene therapy","volume":"1","author":"Jolly","year":"1994","journal-title":"Cancer Gene. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/gt.2009.148","article-title":"Progress and prospects: Immune responses to viral vectors","volume":"17","author":"Nayak","year":"2010","journal-title":"Gene. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.canlet.2018.10.017","article-title":"Adipose tissue-derived mesenchymal stem cells cultured at high density express IFN-beta and TRAIL and suppress the growth of H460 human lung cancer cells","volume":"440\u2013441","author":"Jung","year":"2019","journal-title":"Cancer Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"609","DOI":"10.7150\/ijms.41354","article-title":"Adipose Tissue-Derived Mesenchymal Stem Cells Suppress Growth of Huh7 Hepatocellular Carcinoma Cells via Interferon (IFN)-beta-Mediated JAK\/STAT1 Pathway in vitro","volume":"17","author":"Byun","year":"2020","journal-title":"Int. J. Med. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.canlet.2014.06.018","article-title":"Adipose tissue-derived mesenchymal stem cells cultured at high density express IFN-beta and suppress the growth of MCF-7 human breast cancer cells","volume":"352","author":"Ryu","year":"2014","journal-title":"Cancer Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.immuni.2011.02.006","article-title":"Type I interferon inhibits interleukin-1 production and inflammasome activation","volume":"34","author":"Guarda","year":"2011","journal-title":"Immunity"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Yoo, C.H., Yeom, J.H., Heo, J.J., Song, E.K., Lee, S.I., and Han, M.K. (2014). Interferon beta protects against lethal endotoxic and septic shock through SIRT1 upregulation. Sci. Rep., 4.","DOI":"10.1038\/srep04220"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"495156","DOI":"10.1155\/2013\/495156","article-title":"The effect of inflammatory cytokines in alcoholic liver disease","volume":"2013","author":"Kawaratani","year":"2013","journal-title":"Mediat. Inflamm."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5653","DOI":"10.4049\/jimmunol.180.8.5653","article-title":"Mechanism of IL-1beta-induced increase in intestinal epithelial tight junction permeability","volume":"180","author":"Ye","year":"2008","journal-title":"J. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1016\/j.ajpath.2013.09.001","article-title":"TNF-alpha modulation of intestinal epithelial tight junction barrier is regulated by ERK1\/2 activation of Elk-1","volume":"183","author":"Guo","year":"2013","journal-title":"Am. J. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/s41419-019-1336-4","article-title":"IFNbeta enhances mesenchymal stromal (Stem) cells immunomodulatory function through STAT1-3 activation and mTOR-associated promotion of glucose metabolism","volume":"10","author":"Vigo","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Molnarfi, N., Benkhoucha, M., Bjarnadottir, K., Juillard, C., and Lalive, P.H. (2012). Interferon-beta induces hepatocyte growth factor in monocytes of multiple sclerosis patients. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0049882"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1172\/JCI11808","article-title":"Hepatocyte growth factor ameliorates acute graft-versus-host disease and promotes hematopoietic function","volume":"107","author":"Kuroiwa","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1016\/j.gassur.2003.09.014","article-title":"Hepatocyte growth factor ameliorates inflammatory bowel disease in a rat model","volume":"7","author":"Arthur","year":"2003","journal-title":"J. Gastrointest Surg."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"121","DOI":"10.3109\/00365590903449340","article-title":"Hepatocyte growth factor ameliorates progression of interstitial injuries in tubular epithelial cells","volume":"44","author":"Mou","year":"2010","journal-title":"Scand. J. Urol. Nephrol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1111\/liv.12218","article-title":"Histological improvement following administration of autologous bone marrow-derived mesenchymal stem cells for alcoholic cirrhosis: A pilot study","volume":"34","author":"Jang","year":"2014","journal-title":"Liver Int."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1002\/hep.28693","article-title":"Transplantation with autologous bone marrow-derived mesenchymal stem cells for alcoholic cirrhosis: Phase 2 trial","volume":"64","author":"Suk","year":"2016","journal-title":"Hepatology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1196\/annals.1299.020","article-title":"Involvement of TNF-related apoptosis-inducing ligand (TRAIL) induction in interferon gamma-mediated apoptosis in Ewing tumor cells","volume":"1010","author":"Abadie","year":"2003","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"7081","DOI":"10.4049\/jimmunol.181.10.7081","article-title":"Induction of TRAIL- and TNF-alpha-dependent apoptosis in human monocyte-derived dendritic cells by microfilariae of Brugia malayi","volume":"181","author":"Semnani","year":"2008","journal-title":"J. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1007\/s12010-016-2355-6","article-title":"Effects of A.marina-Derived Isoquercitrin on TNF-Related Apoptosis-Inducing Ligand Receptor (TRAIL-R) Expression and Apoptosis Induction in Cervical Cancer Cells","volume":"182","author":"Arumugam","year":"2017","journal-title":"Appl. Biochem. Biotechnol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s12307-010-0041-8","article-title":"Mesenchymal Stem Cells Overexpressing IFN-beta Inhibit Breast Cancer Growth and Metastases through Stat3 Signaling in a Syngeneic Tumor Model","volume":"3","author":"Ling","year":"2010","journal-title":"Cancer Microenviron."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.3892\/or.2015.4174","article-title":"Bone marrow-derived mesenchymal stem cells co-expressing interleukin-18 and interferon-beta exhibit potent antitumor effect against intracranial glioma in rats","volume":"34","author":"Xu","year":"2015","journal-title":"Oncol. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1002\/hep.30652","article-title":"Fructose Promotes Leaky Gut, Endotoxemia, and Liver Fibrosis Through Ethanol-Inducible Cytochrome P450-2E1-Mediated Oxidative and Nitrative Stress","volume":"73","author":"Cho","year":"2021","journal-title":"Hepatology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.ejmech.2012.12.062","article-title":"Recent advances in natural products from plants for treatment of liver diseases","volume":"63","author":"Zhang","year":"2013","journal-title":"Eur. J. Med. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"889","DOI":"10.2217\/fmb.15.13","article-title":"Systematic review on intervention with prebiotics\/probiotics in patients with obesity-related nonalcoholic fatty liver disease","volume":"10","author":"Tarantino","year":"2015","journal-title":"Future Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1038\/s41375-018-0106-0","article-title":"Clinical use of lentiviral vectors","volume":"32","author":"Milone","year":"2018","journal-title":"Leukemia"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1186\/s13287-019-1488-2","article-title":"Mesenchymal stem cells induce dendritic cell immune tolerance via paracrine hepatocyte growth factor to alleviate acute lung injury","volume":"10","author":"Lu","year":"2019","journal-title":"Stem Cell Res. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"eaay6994","DOI":"10.1126\/sciadv.aay6994","article-title":"In vivo priming of human mesenchymal stem cells with hepatocyte growth factor-engineered mesenchymal stem cells promotes therapeutic potential for cardiac repair","volume":"6","author":"Park","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Boicean, A., Birlutiu, V., Ichim, C., Brusnic, O., and Onisor, D.M. (2023). Fecal Microbiota Transplantation in Liver Cirrhosis. Biomedicines, 11.","DOI":"10.3390\/biomedicines11112930"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/nature14232","article-title":"Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome","volume":"519","author":"Chassaing","year":"2015","journal-title":"Nature"}],"updated-by":[{"DOI":"10.3390\/ijms27188423","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000}}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/15\/8509\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:30:44Z","timestamp":1790008244000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/15\/8509"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,4]]},"references-count":44,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["ijms25158509"],"URL":"https:\/\/doi.org\/10.3390\/ijms25158509","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,4]]}}}