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Gut and Liver

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

Chao Dong*, Han-Jun Li*,, Shi Chang*, Hui-Jun Liao*, Zhi-Peng Zhang*, Peng Huang*, and Hui-Huan Tang*
*Department of General Surgery, Xiangya Hospital, Central South University Xiangya School of Medicine, Changsha, and Department of General Surgery, Wuhan General Hospital of Guangzhou Military Region, Wuhan, China
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
Background/Aims: We aimed to investigate the correlation between a disintegrin and metalloprotease with thrombospondin motif 2 (ADAMTS-2) and transforming growth factor-モ1 (TGF-モ1) 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-モ1. Western blots for other key mediators of cirrhotic progression, including SMAD2, SMAD3, TGF-モ receptor II (TGFモRII), 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-モ1 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 TGFモRII, 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-モ1 may play important roles in the pathogenesis of human cirrhosis; specifically, TGF-モ1 may induce the expression of ADAMTS-2 through the TGFモ/SMAD pathway.
 
KEYWORD
A disintegrin and metalloprotease with thrombospondin motif-2; Transforming growth factor beta 1; Cirrhosis; Humans
 
Gut and Liver 2013 Mar; 7(2): 213-220
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