Hypoxia-Inducible Factors: Regulation and Therapeutic Potential

Dear colleagues,

Molecular oxygen acts as a final electron transfer molecule in oxidative phosphorylation in mitochondria, is deeply involved in oxygen and energy metabolism, and plays a role as a factor in the regulation of iron metabolism, angiogenesis, and vascular tone.

In the late 1980s, a team led by Dr. Gregg L. Semenza in Johns Hopkins University in Baltimore, USA, decided to search for an intracellular factor involved in hypoxia-induced expression of erythropoietin and isolated the cDNA of a transcription factor in 1995. This transcription factor was designated hypoxia-inducible factor 1 (HIF-1). A closely related gene, HIF2A or EPAS1, was identified and cloned in 1997, followed by HIF3A in 1998. A series of genes, such as those coding for various glycolytic enzymes, glucose transport protein, vascular endothelial growth factor, hematopoietic factor erythropoietin, are regulated by HIFs at the transcriptional level. Thus, HIFs play a role beyond the activation of "hypoxia-inducible" genes. We could say that the term “HIF” also stands for "Highly Involved Factor".

We invite research and review papers in various areas of oxygen biology research that focus on, but not exclusively, the fundamental understanding of HIFs signaling pathways and related gene expression profiling, epigenetic regulation, diagnostic, prognostic, and pharmacogenomic biomarkers, molecular targets driving the regulation of human physiology and pathophysiology, clinical trials with new agents, and validation in animal models.

We hope that this Special Issue will reflect our exciting era with respect to the research on HIFs and its applications in medicine and health science.

Prof. Kiichi Hirota
Guest Editor

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