期刊
HEPATOLOGY RESEARCH
卷 26, 期 1, 页码 1-9出版社
WILEY
DOI: 10.1016/S1386-6346(03)00115-3
关键词
CTGF/CCN2; TGF-beta; hepatic stellate cell; extracellular matrix; matricellular; CCN
Connective tissue growth factor (CTGF/CCN2) is a highly profibrogenic molecule which is overexpressed in many fibrotic lesions, including those of the liver. CTGF/CCN2 is transcriptionally activated by transforming growth factor-beta (TGF-beta) and appears to mediate some of the extracellular matrix (ECM)-inducing properties that have been previously attributed to TGF-beta. CTGF/CCN2 and TGF-beta stimulate connective tissue cell proliferation and ECM synthesis in vitro and exhibit shared fibrogenic and angiogenic properties in vivo. In fibrotic liver, CTGF/CCN2 mRNA and protein are produced by fibroblasts, myofibroblasts, hepatic stellate cells (HSCs), endothelial cells, and bile duct epithelial cells. CTGF/CCN2 is also produced at high levels in hepatocytes during cytochrome P-4502E1-mediated ethanol oxidation. CTGF/CCN2 expression in cultured HSCs is enhanced following their activation or stimulation by TGF-beta while exogenous CTGF/CCN2 is able to promote HSC adhesion, proliferation, locomotion, and collagen production. Collectively, these data suggest that during initiating or downstream fibrogenic events in the liver, production of CTGF/CCN2 is regulated primarily by TGF-beta in one or more cell types and that CTGF/CCN2 plays important roles in HSC activation and progression of fibrosis. This article reviews the data that support the importance of CTGF/CCN2 in hepatic fibrosis and highlights the concept that CTGF/CCN2 may represent a new therapeutic target in this disease. (C) 2003 Elsevier Science B.V. All rights reserved.
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