The cellular response to hypoxia: tuning the system with microRNAs

Abstract

Adaptation to hypoxia is an essential cellular response controlled by the oxygen-sensitive master transcription factor hypoxia-inducible factor 1 (HIF-1). HIF-1 expression is also controlled by specific microRNAs and, in turn, controls the expression of other microRNAs, which fine-tune adaptation to low oxygen tension. In this issue of the JCI, Ghosh and colleagues identify a unique microRNA in hypoxic endothelial cells, miR424, that promotes HIF-1 stabilization and angiogenesis. The actions of this microRNA are considered in the context of the complex interactions that act to ensure optimal endothelial adaptation to this critical environmental condition.

Figure 1. The endothelial cell response to hypoxia.

The endothelium is poised between flowing blood and metabolizing tissue. Under the hypoxic (ischemic) conditions accompanying reductions in blood flow, the endothelial response is governed by HIF, as well as hypoxamirs, which are themselves either induced by HIF or affect HIF expression and action. The net effect is a metabolic switch to glycolysis and endothelial proliferation and differentiation, actions that facilitate durable adaptation to hypoxia sufficient to promote angiogenesis and restore blood flow. The text highlighted in the blue rectangle indicates how the work of Ghosh and colleagues integrates with current understanding of hypoxamirs.