title: Smad3 deficiency ameliorates hepatic fibrogenesis through the expression of senescence marker protein-30, an antioxidant-related protein.
abstract: 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.
authors.affiliation: Department of Pathology, College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Korea. jeongks@knu.ac.kr.
authors.forename: Da-Hee
authors.initials: DH
authors.lastname: Jeong
authors.forename: Meeyul
authors.initials: M
authors.lastname: Hwang
authors.forename: Jin-Kyu
authors.initials: JK
authors.lastname: Park
authors.forename: Moon-Jung
authors.initials: MJ
authors.lastname: Goo
authors.forename: Il-Hwa
authors.initials: IH
authors.lastname: Hong
authors.forename: Mi-Ran
authors.initials: MR
authors.lastname: Ki
authors.forename: Akihito
authors.initials: A
authors.lastname: Ishigami
authors.forename: Ah-Young
authors.initials: AY
authors.lastname: Kim
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Lee
authors.forename: Eun-Joo
authors.initials: EJ
authors.lastname: Lee
authors.forename: Kyu-Shik
authors.initials: KS
authors.lastname: Jeong
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002251:Carbon Tetrachloride / Q000633:toxicity; D015180:Electrophoresis, Gel, Two-Dimensional; D005982:Glutathione Transferase / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D040901:Proteomics; D011956:Receptors, Cell Surface / Q000378:metabolism; D012720:Severity of Illness Index; D015398:Signal Transduction; D051900:Smad3 Protein / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D002135:Calcium-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011956:Receptors, Cell Surface; C513324:Rgn protein, mouse; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; C094480:sp56 protein, mouse; D002251:Carbon Tetrachloride; D005982:Glutathione Transferase