Stabilization of hepatocyte growth factor mRNA by hypoxia-inducible factor 1

Mol Biol Rep. 2009 Sep;36(7):1967-75. doi: 10.1007/s11033-008-9406-1. Epub 2008 Nov 2.


Hypoxia regulates expression of hepatocyte growth factor (HGF) by increasing its transcription and by stabilizing its mRNA. Despite the pivotal role of hypoxia-inducible factor 1 (HIF-1) in transcriptional activation of hypoxia-responsive genes, it is not known whether HIF-1 mediates hypoxia-induced stabilization of HGF mRNA. We constructed adenoviral vectors expressing either the wild-type HIF-1alpha (Ad2/HIF-1alpha/FL), a constitutively stable hybrid form of HIF-1alpha (Ad2/HIF-1alpha/VP16), or no transgene (Ad2/CMVEV). In rat glioma (C6) cells, human glioma (U251) cells human cardiac, vascular smooth muscle, and endothelial cells, infection with Ad2/HIF-1alpha/VP16 or Ad2/HIF-1alpha/FL increased HGF expression at both the mRNA and protein levels. Under normoxic conditions, the half-life of HGF mRNA was 43 min in C6 and U251 cells. Hypoxia and Ad2/HIF-1alpha/VP16 increased the half-life of HGF mRNA to 3.2 and 2.8 h, respectively, while Ad2/CMVEV had no effect. These studies are the first to demonstrate that overexpression of HIF-1alpha increases HGF mRNA stability. Our results also suggest that stabilization of HGF mRNA by hypoxia is mediated, at least in part, by HIF-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / metabolism
  • Animals
  • Cell Hypoxia
  • Cell Line, Tumor
  • Endothelial Cells / metabolism
  • Gene Expression Regulation, Neoplastic
  • Hepatocyte Growth Factor / genetics*
  • Hepatocyte Growth Factor / metabolism
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Myocardium / cytology
  • Myocardium / metabolism
  • Myocytes, Smooth Muscle / metabolism
  • RNA Stability*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats


  • Hypoxia-Inducible Factor 1, alpha Subunit
  • RNA, Messenger
  • Hepatocyte Growth Factor