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


CONCLUSIONS
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.
Zhang
Yi
Y
Department of Gastroenterology, Union Hospital, Tongji Medical Collage, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Liu
Ping
P
Gao
Xiaoliang
X
Qian
Wei
W
Xu
Keshu
K
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001706:Biopsy; D024042:Collagen Type I / Q000096:biosynthesis*; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D053782:Transforming Growth Factor beta3 / Q000235:genetics / Q000494:pharmacology*
D024042:Collagen Type I; D011994:Recombinant Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1; D053782:Transforming Growth Factor beta3; D049452:Green Fluorescent Proteins; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9