Hypoxia induces the activation of human hepatic stellate cells LX-2 through TGF-beta 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-1alpha and VEGF gene was induced. The result of Western blotting showed that the expression of alpha-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-beta/Smad signaling pathway showed that hypoxia potentiated the expression of TGF-beta1 and the phosphorylation status of Smad2. Gene expression profiles of LX-2 cells induced by hypoxia were obtained by using cDNA microarray technique.
Shi
Yue-Feng
YF
Department of Biology and Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong, China.
Fong
Chi-Chun
CC
Zhang
Qi
Q
Cheung
Pik-Yuen
PY
Tzang
Chi-Hung
CH
Wu
Rudolf S S
RS
Yang
Mengsu
M
D000693:Anaerobiosis / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D008099:Liver / Q000166:cytology* / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D015398:Signal Transduction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D020778:Matrix Metalloproteinase 2