| First Author | Niu L | Year | 2016 |
| Journal | PLoS One | Volume | 11 |
| Issue | 5 | Pages | e0156090 |
| PubMed ID | 27224286 | Mgi Jnum | J:248892 |
| Mgi Id | MGI:6094608 | Doi | 10.1371/journal.pone.0156090 |
| Citation | Niu L, et al. (2016) Involvement of TGF-beta1/Smad3 Signaling in Carbon Tetrachloride-Induced Acute Liver Injury in Mice. PLoS One 11(5):e0156090 |
| abstractText | Transforming growth factor-beta1 (TGF-beta1) is a major factor in pathogenesis of chronic hepatic injury. Carbon tetrachloride (CCl4) is a liver toxicant, and CCl4-induced liver injury in mouse is a classical animal model of chemical liver injury. However, it is still unclear whether TGF-beta1 is involved in the process of CCl4-induced acute chemical liver injury. The present study aimed to evaluate the role of TGF-beta1 and its signaling molecule Smad3 in the acute liver injury induce by CCl4. The results showed that CCl4 induced acute liver injury in mice effectively confirmed by H&E staining of liver tissues, and levels of not only liver injury markers serum ALT and AST, but also serum TGF-beta1 were elevated significantly in CCl4-treated mice, compared with the control mice treated with olive oil. Our data further revealed that TGF-beta1 levels in hepatic tissue homogenate increased significantly, and type II receptor of TGF-beta (TbetaRII) and signaling molecules Smad2, 3, mRNA expressions and Smad3 and phospho-Smad3 protein levels also increased obviously in livers of CCl4-treated mice. To clarify the effect of the elevated TGF-beta1/Smad3 signaling on CCl4-induced acute liver injury, Smad3 in mouse liver was overexpressed in vivo by tail vein injection of Smad3-expressing plasmids. Upon CCl4 treatment, Smad3-overexpressing mice showed more severe liver injury identified by H&E staining of liver tissues and higher serum ALT and AST levels. Simultaneously, we found that Smad3-overexpressing mice treated with CCl4 showed more macrophages and neutrophils infiltration in liver and inflammatory cytokines IL-1beta and IL-6 levels increment in serum when compared with those in control mice treated with CCl4. Moreover, the results showed that the apoptosis of hepatocytes increased significantly, and apoptosis-associated proteins Bax, cytochrome C and the cleaved caspase 3 expressions were up-regulated in CCl4-treated Smad3-overexpressing mice as well. These results suggested that TGF-beta1/Smad3 signaling was activated during CCl4-induced acute liver injury in mice, and Smad3 overexpression aggravated acute liver injury by promoting inflammatory cells infiltration, inflammatory cytokines release and hepatocytes apoptosis. In conclusion, the activation of TGF-beta signaling contributes to the CCl4-induced acute liver injury. Thus, TGF-beta1/Smad3 may serve as a potential target for acute liver injury therapy. |
