The Role of NF-?B in Hypoxia-Induced Gene Expression
Hypoxia is a common physiologic and pathophysiologic stimulus that activates the expression of genes through oxygen-sensitive transcription factors including the hypoxia-inducible factor (HIF) and nuclear factor-kappaB (NF-?B). Hypoxia-dependent gene expression can have important physiologic or pathophysiologic consequences for an organism, depending upon the cause of the hypoxic insult. Consequently, this pathway represents an attractive therapeutic target in a number of disease states. While the mechanism linking hypoxia to the activation of HIF has been extensively studied, our understanding of how hypoxia activates NF-?B is limited. Recent studies have demonstrated that similar oxygen-sensing mechanisms are employed in conferring oxygen sensitivity to both HIF and NF-?B?dependent gene expression. Furthermore, there is an extensive degree of cross-talk occurring between NF-?B and HIF. Investigations into mechanisms of hypoxic activation of HIF and NF-?B and how these signaling pathways interact will uncover new therapeutic modalities in a diverse range of disease states where hypoxia is a feature of the microenvironment including cancer, vascular disease, and chronic inflammation.
hypoxia hypoxia-inducible factor (hif) nuclear factor-kappab (nf-?b) inflammation