HIF in Kidney Disease and Development

Tissue hypoxia is a pathologic feature of many human diseases including cancer, myocardial infarction, stroke, and kidney disease. An evolutionarily conserved oxygen-sensing mechanism enables cells to adapt and maintain homeostasis under hypoxic conditions by transcriptional activation of a host of genes that mediate metabolic adaptation, angiogenesis, energy conservation, erythropoiesis, and cell survival. The hypoxia-inducible factors (HIFs) comprise a family of oxygen-sensitive basic helix-loop-helix proteins that control the cellular transcriptional response to hypoxia. Inappropriate activation of the HIF system is linked to the development and/or progression of many human malignancies including clear cell renal cancer. HIFs are now postulated to play contrasting protective and pathogenic roles in acute and chronic kidney diseases, respectively. In this review, we discuss the mechanisms of oxygen sensing in renal cells and highlight the role of hypoxia and HIF activation under physiologic conditions and in renal development as well as in acute and chronic kidney diseases.