[The roles of hypoxia signaling in tissue remodeling]

A molecular oxygen is essential to keep a physiological activity of each organ or a cell. There exists a heterogeneity in a level of oxygen concentration in each organ. In addition, tissue oxygen concentration fluctuates dynamically during physiological activities or in pathological processes. A decrease in tissue oxygen concentration, termed as hypoxia, significantly influences the function in each organ or cell. For example, a transcript level in each gene tends to be reduced under hypoxic condition. On the other hand, some of the gene expressions are increased significantly in hypoxia, which are termed as hypoxia responsive genes. A group of transcription factor, hypoxia inducible factor (HIF)-1α and HIF-2α play a critical role in the transactivation processes of hypoxia responsive genes. Recently, the molecular processes have been elucidated by which hypoxic environment activates HIF-1α or HIF-2α activity. A preclinical animal model revealed that HIF-α signal plays a critical role in inflammation or tissue remodeling. While HIF-1α and HIF-2α usually work synergistically in inducing their target gene expressions, macrophage HIF-1α and HIF-2α act antagonistically with regard to the synthesis of nitric oxide, a potent inflammatory mediator. This review summarizes the current understanding on the roles of HIF-α mediated hypoxic responses in inflammation or tissue remodeling.