Hypoxia induces the activation of human hepatic stellate cells LX-2 through TGF-β signaling pathway

Hypoxia is a common environmental stress factor and is also associated with various physiological and pathological conditions such as fibrogenesis. The activation of hepatic stellate cells (HSCs) is the key event in the liver fibrogenesis. In this study, the behavior of human HSCs LX-2 in low oxygen tension (1% O₂) was analyzed. Upon hypoxia, the expression of HIF-1α and VEGF gene was induced. The result of Western blotting showed that the expression of α-SMA was increased by hypoxic stimulation. Furthermore, the expression of MMP-2 and TIMP-1 genes was increased. Hypoxia also elevated the protein expression of the collagen type I in LX-2 cells. The analysis of TGF-β/Smad signaling pathway showed that hypoxia potentiated the expression of TGF-β1 and the phosphorylation status of Smad2. Gene expression profiles of LX-2 cells induced by hypoxia were obtained by using cDNA microarray technique. Copyright © 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.