rAAV2-TGF-β(3) decreases collagen synthesis and deposition in the liver of experimental hepatic fibrosis rat

Dig Dis Sci. 2010 Oct;55(10):2821-30. doi: 10.1007/s10620-009-1119-3. Epub 2010 Jan 28.

Abstract

Background/aims: Hepatic fibrosis is one kind of common wound-healing response to chronic liver injury. Transforming growth factor (TGF)-β(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-β(3) on the histology in the liver of rat with liver fibrosis.

Methods: Recombinantadeno-associated virus (rAAV) 2-TGF-β(3) and rAAV2-EGFP were constructed. Rats were randomly divided into normal control group, model group, negative control group and TGF-β(3) treated group. The hepatic fibrosis model was induced by CCl(4) administration. We injected a single dose of either rAAV2-TGF-β(3) or rAAV2-EGFP into the TGF-β(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.

Results: With the treatment of TGF-β(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).

Conclusion: rAAV2-TGF-β(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-β(3)-based therapy for hepatic fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Biopsy
  • Collagen Type I / biosynthesis*
  • Disease Models, Animal
  • Extracellular Matrix / metabolism
  • Green Fluorescent Proteins / genetics
  • Immunohistochemistry
  • Liver / metabolism
  • Liver / pathology
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / pathology
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / genetics
  • Recombinant Proteins / pharmacology*
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Transforming Growth Factor beta3 / genetics
  • Transforming Growth Factor beta3 / pharmacology*

Substances

  • Collagen Type I
  • Recombinant Proteins
  • Tissue Inhibitor of Metalloproteinase-1
  • Transforming Growth Factor beta3
  • Green Fluorescent Proteins
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9