Gut Liver.  2013 Mar;7(2):213-220.

A Disintegrin and Metalloprotease with Thrombospondin Motif 2 May Contribute to Cirrhosis in Humans through the Transforming Growth Factor-beta/SMAD Pathway

• Dong C
• Li HJ
• Chang S
• Liao HJ
• Zhang ZP
• Huang P
• Tang HH

Abstract

BACKGROUND/AIMS
We aimed to investigate the correlation between a disintegrin and metalloprotease with thrombospondin motif 2 (ADAMTS-2) and transforming growth factor-beta1 (TGF-beta1) in clinical human cirrhotic tissues.
METHODS
The liver tissues of 24 patients (16 cases with cirrhotic portal hypertension as the cirrhosis group and eight cases with healthy livers as the normal group) were collected. Immunohistochemistry and Western blots were performed to evaluate the protein expression levels of ADAMTS-2 and TGF-beta1. Western blots for other key mediators of cirrhotic progression, including SMAD2, SMAD3, TGF-beta receptor II (TGFbetaRII), matrix metalloproteinases 2 (MMP2), and tissue inhibitor of matrix metalloproteinases 2 (TIMP2), were also performed.
RESULTS
Cirrhotic tissues showed higher percentages of collagen. The protein expression levels of ADAMTS-2 and TGF-beta1 were significantly higher in the cirrhotic group as compared to the matched normal group (p<0.05), and there was a positive correlation between these two proteins (r=0.862, p<0.01). The protein expressions of MMP2, TIMP2, and TGFbetaRII, as well as the phosphorylated forms of SMAD2 and SMAD3, were significant higher in the cirrhotic group (p<0.01 or p<0.05).
CONCLUSIONS
These findings suggested that ADAMTS-2 and TGF-beta1 may play important roles in the pathogenesis of human cirrhosis; specifically, TGF-beta1 may induce the expression of ADAMTS-2 through the TGFbeta/SMAD pathway.

Keyword

A disintegrin and metalloprotease with thrombospondin motif-2; Transforming growth factor beta 1; Cirrhosis; Humans

MeSH Terms

Blotting, Western
Collagen
Fibrosis
Humans
Hypertension, Portal
Immunohistochemistry
Liver
Matrix Metalloproteinases
Proteins
Receptors, Transforming Growth Factor beta
Thrombospondins
Transforming Growth Factor beta1
Collagen
Matrix Metalloproteinases
Proteins
Receptors, Transforming Growth Factor beta
Thrombospondins
Transforming Growth Factor beta1