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Widespread, hypoxia‐inducible expression of HIF‐2α in distinct cell populations of different organs

Widespread, hypoxia‐inducible expression of HIF‐2α in distinct cell populations of different organs

Authors :
Peter J. Ratcliffe
Michael S. Wiesener
Stefano J. Mandriota
Christopher W. Pugh
Christian Rosenberger
Charlotte K Scholze
Ingo Bechmann
Jan Hörstrup
Kai-Uwe Eckardt
Patrick H. Maxwell
Sebastian Bachmann
Jan Steffen Jürgensen
Ulrich Frei
Christina Warnecke
Source :
The FASEB Journal. 17:271-273
Publication Year :
2002
Publisher :
Wiley, 2002.

Abstract

Cellular responses to oxygen are increasingly recognized as critical in normal development and physiology, and are implicated in pathological processes. Many of these responses are mediated by the transcription factors HIF-1 and HIF-2. Their regulation occurs through oxygen-dependent proteolysis of the alpha subunits HIF-1alpha and HIF-2alpha, respectively. Both are stabilized in cell lines exposed to hypoxia, and recently HIF-1alpha was reported to be widely expressed in vivo. In contrast, regulation and sites of HIF-2alpha expression in vivo are unknown, although a specific role in endothelium was suggested. We therefore analyzed HIF-2alpha expression in control and hypoxic rats. Although HIF-2alpha was not detectable under baseline conditions, marked hypoxic induction occurred in all organs investigated, including brain, heart, lung, kidney, liver, pancreas, and intestine. Time course and amplitude of induction varied between organs. Immunohistochemistry revealed nuclear accumulation in distinct cell populations of each tissue, which were exclusively non-parenchymal in some organs (kidney, pancreas, and brain), predominantly parenchymal in others (liver and intestine) or equally distributed (myocardium). These data indicate that HIF-2 plays an important role in the transcriptional response to hypoxia in vivo, which is not confined to the vasculature and is complementary to rather than redundant with HIF-1.

Details

ISSN :
15306860 and 08926638
Volume :
17
Database :
OpenAIRE
Journal :
The FASEB Journal
Accession number :
edsair.doi.dedup.....5d607ce589c8a09fb0babae2e95bc886
Full Text :
https://doi.org/10.1096/fj.02-0445fje