Potential role of hypoxia in development versus disease. Potential role of hypoxia in development versus disease. Reduced oxygen tension induces the stabilization of the HIF1α protein, enabling heterodimerization with HIF1β to enable HIF-mediated transcriptional regulation. This transcriptional complex is known to intersect with key signaling pathways, including Wnt and Notch signaling.123,124 Hypoxia is a common component of AKI. During development, the oxygen tension at the tissue level is also low, with this physiologic hypoxia important for optimal morphogenesis.105In vitro and in vivo studies suggest that further reductions or indeed elevations in oxygen tension adversely affect development.105,109,110 It is likely that other transcription factors active during development also respond to this reduced oxygen tension. The transcriptional similarities between normal development and acute injury may therefore reflect the similarities in oxygen tension. Melissa Helen Little, and Pamela Kairath JASN 2017;28:34-46 ©2017 by American Society of Nephrology