rAAV2-TGF-β3 Decreases Collagen Synthesis and Deposition in the Liver of Experimental Hepatic Fibrosis Rat

Hepatic fibrosis is one kind of common wound-healing response to chronic liver injury. Transforming growth factor (TGF)-beta(3) performs an anti-fibrosis function under certain conditions such as pancreatic fibrosis and wound healing. This study aimed at investigating the effect of TGF-beta(3) on the histology in the liver of rat with liver fibrosis. Recombinantadeno-associated virus (rAAV) 2-TGF-beta(3) and rAAV2-EGFP were constructed. Rats were randomly divided into normal control group, model group, negative control group and TGF-beta(3) treated group. The hepatic fibrosis model was induced by CCl4 administration. We injected a single dose of either rAAV2-TGF-beta(3) or rAAV2-EGFP into the TGF-beta(3) group and the negative control group. The histopathologic changes of liver were determined by hematoxylin and eosin (HE) staining and Masson staining. The expressions of type I collagen, MMP-9, MMP-2, and TIMP-1 in liver were detected by Immunohistochemical staining. With the treatment of TGF-beta(3), the degree of fibrosis and the deposition of collagen fiber in liver were markedly reduced, and the expression of MMP-9 was obviously increased (P < 0.001), while type I collagen and TIMP-1 were decreased (P = 0.004, P = 0.001) compared with the model group, but the expressed difference of MMP-2 had no statistical significance (P = 0.180). rAAV2-TGF-beta(3) reduces the histopathologic damage of liver fibrosis on rats, and it may suppress the synthesis and deposition of type I collagen by regulating the expressions of matrix metalloproteinases and their inhibitors. Potentially, our findings might help with the design of a new TGF-beta(3)-based therapy for hepatic fibrosis.