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

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.

• Authors: Yi Zhang, Ping Liu, Xiaoliang Gao, Wei Qian, Keshu Xu
• Journal: Digestive diseases and sciences (Dig Dis Sci) Vol. 55 Issue 10 Pg. 2821-30 (Oct 2010) ISSN: 1573-2568 [Electronic] United States
• PMID: 20108118 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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