{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:24:35Z","timestamp":1790717075889,"version":"4.1.0"},"reference-count":20,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2013,12,4]],"date-time":"2013-12-04T00:00:00Z","timestamp":1386115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Smad3 is a key mediator of the transforming growth factor (TGF)-\u03b21 signaling pathway that plays central role in inflammation and fibrosis. In present study, we evaluated the effect of Smad3 deficiency in Smad3\u2212\/\u2212 mice with carbon tetrachloride (CCl4)-induced liver fibrosis. The animals were received CCl4 or olive oil three times a week for 4 weeks. Histopathological analyses were performed to evaluate the fibrosis development in the mice. Alteration of protein expression controlled by Smad3 was examined using a proteomic analysis. CCl4-induced liver fibrosis was rarely detected in Smad3\u2212\/\u2212 mice compared to Smad3+\/+. Proteomic analysis revealed that proteins related to antioxidant activities such as senescence marker protein-30 (SMP30), selenium-binding proteins (SP56) and glutathione S-transferases (GSTs) were up-regulated in Smad3\u2212\/\u2212 mice. Western blot analysis confirmed that SMP30 protein expression was increased in Smad3\u2212\/\u2212 mice. And SMP30 levels were decreased in CCl4-treated Smad3+\/+ and Smad3\u2212\/\u2212 mice. These results indicate that Smad3 deficiency influences the proteins level related to antioxidant activities during early liver fibrosis. Thus, we suggest that Smad3 deteriorate hepatic injury by inhibitor of antioxidant proteins as well as mediator of TGF-\u03b21 signaling.<\/jats:p>","DOI":"10.3390\/ijms141223700","type":"journal-article","created":{"date-parts":[[2013,12,4]],"date-time":"2013-12-04T12:02:38Z","timestamp":1386158558000},"page":"23700-23710","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Smad3 Deficiency Ameliorates Hepatic Fibrogenesis through  the Expression of Senescence Marker Protein-30,  an Antioxidant-Related Protein"],"prefix":"10.3390","volume":"14","author":[{"given":"Da-Hee","family":"Jeong","sequence":"first","affiliation":[{"name":"Department of Pathology, College of Veterinary Medicine, Kyungpook National University,  Daegu 702-701, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meeyul","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Veterinary Medicine, Kyungpook National University,  Daegu 702-701, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Kyu","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Veterinary Medicine, Kyungpook National University,  Daegu 702-701, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moon-Jung","family":"Goo","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Veterinary Medicine, Kyungpook National University,  Daegu 702-701, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Il-Hwa","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Veterinary Medicine, Kyungpook National University,  Daegu 702-701, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi-Ran","family":"Ki","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Veterinary Medicine, Kyungpook National University,  Daegu 702-701, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihito","family":"Ishigami","sequence":"additional","affiliation":[{"name":"Aging Regulation, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0600-1816","authenticated-orcid":false,"given":"Ah-Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Veterinary Medicine, Kyungpook National University,  Daegu 702-701, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun-Mi","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Veterinary Medicine, Kyungpook National University,  Daegu 702-701, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun-Joo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Veterinary Medicine, Kyungpook National University,  Daegu 702-701, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyu-Shik","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Veterinary Medicine, Kyungpook National University,  Daegu 702-701, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2013,12,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"196","DOI":"10.3109\/08977194.2011.595714","article-title":"TGF-\u03b2 signaling in fibrosis","volume":"29","author":"Biernacka","year":"2011","journal-title":"Growth Factors"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s00441-011-1246-y","article-title":"TGF-\u03b2 in progression of liver disease","volume":"347","author":"Dooley","year":"2012","journal-title":"Cell Tissue Res"},{"key":"ref_3","first-page":"1","article-title":"Roles of TGF\u03b2 signaling Smads in squamous cell carcinoma","volume":"28","author":"Han","year":"2011","journal-title":"Cell Biosci"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s00441-011-1178-6","article-title":"Smad phosphoisoform signals in acute and chronic liver injury: Similarities and differences between epithelial and mesenchymal cells","volume":"347","author":"Matsuzaki","year":"2012","journal-title":"Cell Tissue Res"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1002\/jcp.20215","article-title":"Selective reduction of fibrotic markers in repairing corneas of mice deficient in Smad3","volume":"203","author":"Stramer","year":"2005","journal-title":"J. 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