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

Yue-Feng SHI, Chi-Chun FONG, Qi ZHANG, Pik-Yuen CHEUNG, Chi-Hung TZANG, Shiu Sun Rudolf WU, Mengsu YANG

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Abstract

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.

Original languageEnglish
Pages (from-to)203-210
JournalFEBS Letters
Volume581
Issue number2
DOIs
Publication statusPublished - 23 Jan 2007

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Hepatic Stellate Cells
Genes
Chemical activation
Phosphorylation
Tissue Inhibitor of Metalloproteinase-1
Microarrays
Collagen Type I
Matrix Metalloproteinases
Gene expression
Liver
Vascular Endothelial Growth Factor A
Complementary DNA
Oxygen
Cell Hypoxia
Oligonucleotide Array Sequence Analysis
Transcriptome
Proteins
Western Blotting
Hypoxia

Citation

Shi, Y.-F., Fong, C.-C., Zhang, Q., Cheung, P.-Y., Tzang, C.-H., Wu, R. S. S., & Yang, M. (2007). Hypoxia induces the activation of human hepatic stellate cells LX-2 through TGF-β signaling pathway. FEBS Letters, 581(2), 203-210. doi: 10.1016/j.febslet.2006.12.010

Keywords

  • Hypoxia
  • Hepatic stellate cells
  • Fibrogenesis
  • HSCs
  • TGF-β1
  • Transforming growth factor-β1
  • ECM
  • Extracellular matrix
  • MMP
  • Metalloproteinase
  • TIMP
  • Tissue inhibitor of metalloproteinase