Oxygen-regulated expression of the Wilms' tumor suppressor Wt1 involves hypoxia-inducible factor-1 (HIF-1).

SPECIFIC AIMSWe recently reported de novo expression of the Wilms’ tumor suppressor Wt1, a critical molecule for development of the heart and genitourinary system, in blood vessels of the ischemic myocardium. The purpose of this study was to analyze the mechanism(s) of hypoxic/ischemic induction of Wt1 and to assess the potential impact of oxygen-regulated Wt1 expression.PRINCIPAL FINDINGS1. Wt1 mRNA in normoxic and hypoxic organsRNase protection assay was used to measure Wt1 mRNA in various organs of rats exposed at normal atmosphere (20% O2) or at normobaric hypoxia (8% O2). Hypoxic exposure increased Wt1 transcripts in the kidneys and heart on average 3.3- and 2.3-fold (n=5, each) compared with rats at normoxia (20% O2). A significant increase of Wt1 mRNA was detectable after 2 h of oxygen restriction and could be mimicked by exposure at 0.1% carbon monoxide. No differences in Wt1 mRNA were found in the brain and spleen of normoxic and hypoxic rats.2. Wt1 is expressed de novo in the tubules of hypoxic ...