Hypoxia-inducible factors and kidney vascular development.

Abstract

Among the genes strongly induced by hypoxia-inducible factors (HIF) and highly expressed during kidney microvascular development is vascular endothelial growth factor, which encodes a potent endothelial mitogen and chemoattractant critical for embryonic vasculogenesis and angiogenesis. In developing kidney, glomerular podocytes are particularly rich sources of vascular endothelial growth factor, which probably serves to attract endothelial precursors into vascular clefts of immature glomeruli, promote their mitosis and differentiation into glomerular endothelial cells, and assist with maintenance of their highly differentiated state through maturation. This article summarizes the structure, function, and expression of HIF and discusses HIF target genes expressed during kidney vascular development. Furthermore, it is speculated that different HIF heterodimers are stabilized in different cell populations, which may lead to cell-selective induction of HIF target genes important for renal vasculogenesis/angiogenesis.