Conditional hypoxia inducible factor-1α induction in embryonic pulmonary epithelium impairs maturation and augments lymphangiogenesis.

ABSTRACT: Hypoxia inducible factor (HIF) 1a, EPAS1 and NEPAS are expressed in the embryonic mouse lung and each isoform exhibits distinct spatiotemporal expression patterns throughout morphogenesis. To further assess the role of the HIF1a isoform in lung epithelial cell differentiation and homeostasis, we created transgenic mice that express a constitutively active isoform of human HIF-1a (HIF-1a three point mutant (TPM)), in a doxycycline-dependent manner. Expression of HIF1a TPM in the developing pulmonary epithelium resulted in lung hypoplasia characterized by defective branching morphogenesis, altered cellular energetics and impaired epithelial maturation, culminating in neonatal lethality at birth from severe respiratory distress. Histological and biochemical analyses revealed expanded glycogen

SUBMITTER: Bridges JP 

PROVIDER: S-EPMC3262673 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature