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

BACKGROUND/AIMS We aimed to investigate the correlation between a disintegrin and metalloprotease with thrombospondin motif 2 (ADAMTS-2) and transforming growth factor-β1 (TGF-β1) 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-β1. Western blots for other key mediators of cirrhotic progression, including SMAD2, SMAD3, TGF-β receptor II (TGFβRII), 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-β1 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 TGFβRII, 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-β1 may play important roles in the pathogenesis of human cirrhosis; specifically, TGF-β1 may induce the expression of ADAMTS-2 through the TGFβ/SMAD pathway.