Volume 16 Issue 6, June 2006: 548-558
ORIGINAL ARTICLES
Hypoxia upregulates hypoxia inducible factor (HIF)-3α expression in lung epithelial cells: characterization and comparison with HIF-1α
Qi Fang Li, Xiang Rui Wang, Yue Wu Yang, Han Lin
1Department of Anesthesiology, Renji Hospital, Shanghai Second Medical University, 1630 Dongfang Road, Shanghai 200127, China
Correspondence: Xiang Rui Wang(xiangruiwang@yahoo.com.cn)
The role of the hypoxia-inducible factor (HIF) subunits 1a and 2a in response to hypoxia is well established in lung
epithelial cells, whereas little is known about
HIF-3α with respect to transcriptional and translational regulation by hypoxia.
HIF-3α and
HIF-1α are two similar but distinct basic helix-loop-helix-PAS proteins, which have been postulated
to activate hypoxia responsive genes in response to hypoxia. Here, we used quantitative real time RT-PCR and immunoblotting
to determine the activation of
HIF-3α vs.
HIF-1α by hypoxia.
HIF-3α was strongly induced by hypoxia (1%
O
2) both at the level of protein and mRNA due to an increase in protein stability and transcriptional activation, whereas
HIF-1α protein and mRNA levels enhanced transiently and then decreased because of a reduction in its mRNA stability
in A549 cells, as measured on mRNA and protein levels. Interestingly,
HIF-3α and
HIF-1α exhibited strikingly similar
responses to a variety of activating or inhibitory pharmacological agents. These results demonstrate that
HIF-3α is expressed
abundantly in lung epithelial cells, and that the transcriptional induction of
HIF-3α plays an important role in the
response to hypoxia in vitro. Our findings suggest that
HIF-3α, as a member of the HIF system, is complementary rather
than redundant to
HIF-1α induction in protection against hypoxic damage in alveolar epithelial cells.
Cell Research (2006) 16:548-558. doi:10.1038/sj.cr.7310072; published online 15 June 2006
Keywords: hypoxia inducible factor, alveolar epithelial type II cells, hypoxia, gene expression, in vitro
Cell Research (2006) 16:548-558. doi:10.1038/sj.cr.7310072; published online 15 June 2006
FULL TEXT | PDF
Browse 1905
