Premium
Up‐regulation of gene expression by hypoxia is mediated predominantly by hypoxia‐inducible factor 1 (HIF‐1)
Author(s) -
Greijer AE,
van der Groep P,
Kemming D,
Shvarts A,
Semenza GL,
Meijer GA,
van de Wiel MA,
Belien JAM,
van Diest PJ,
van der Wall E
Publication year - 2005
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1778
Subject(s) - biology , gene , hypoxia (environmental) , gene expression , microbiology and biotechnology , regulation of gene expression , hypoxia inducible factors , genetics , chemistry , organic chemistry , oxygen
The hypoxia‐inducible factor 1 (HIF‐1) plays a critical role in cellular responses to hypoxia. The aim of the present study was to evaluate which genes are induced by hypoxia, and whether this induction is mediated by HIF‐1, by expression microarray analysis of wt and HIF‐1α null mouse fibroblasts. Forty‐five genes were up‐regulated by hypoxia and 40 (89%) of these were regulated by HIF‐1. Of the 114 genes down‐regulated by hypoxia, 19 (17%) were HIF‐1‐dependent. All glycolytic enzymes were strongly up‐regulated by hypoxia in a HIF‐1‐dependent manner. Genes already known to be related to hypoxia, such as glucose transporter 1, BNIP3, and hypoxia‐induced gene 1, were induced. In addition, multiple new HIF‐1‐regulated genes were identified, including genes involved in metabolism (adenylate kinase 4, galactokinase), apoptosis (galectin‐3 and gelsolin), and invasion (RhoA). Genes down‐regulated by hypoxia were involved in cytoskeleton maintenance (Rho kinase), mRNA processing (heterogeneous nuclear ribonucleoprotein H1 and splicing factor), and DNA repair (REV3). Furthermore, seven cDNAs from genes with unknown function or expressed sequence tags (ESTs) were up‐regulated and 27 such cDNAs were down‐regulated. In conclusion, hypoxia causes down‐ rather than up‐regulation of gene expression and HIF‐1 seems to play a major role in the regulation of hypoxia‐induced genes. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.