Smad3 Deficiency Ameliorates Hepatic Fibrogenesis through the Expression of Senescence Marker Protein-30, an Antioxidant-Related Protein

International Journal of Molecular Sciences

Da-Hee Jeong²  Meeyul Hwang²  Jin-Kyu Park²  Moon-Jung Goo²  Il-Hwa Hong²  Mi-Ran Ki²  Akihito Ishigami¹  Ah-Young Kim²  Eun-Mi Lee²  Eun-Joo Lee² 

[1] Aging Regulation, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan; E-Mail:;Department of Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Korea; E-Mails:

关键词: liver fibrosis;    Smad3;    SMP-30;    antioxidant;   

DOI  :  10.3390/ijms141223700

来源: mdpi

【 摘 要 】

Smad3 is a key mediator of the transforming growth factor (TGF)-β1 signaling pathway that plays central role in inflammation and fibrosis. In present study, we evaluated the effect of Smad3 deficiency in Smad3^−/− 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^−/− 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^−/− mice. Western blot analysis confirmed that SMP30 protein expression was increased in Smad3^−/− mice. And SMP30 levels were decreased in CCl₄-treated Smad3^+/+ and Smad3^−/− 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-β1 signaling.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland