Hypoxia signaling in human diseases and therapeutic targets

Autor: Jae W. Lee, Cynthia Ju, Holger K. Eltzschig, Junsuk Ko
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Experimental and Molecular Medicine, Vol 51, Iss 6, Pp 1-13 (2019)
Experimental & Molecular Medicine
ISSN: 2092-6413
1226-3613
Popis: Since the discovery of hypoxia-inducible factor (HIF), numerous studies on the hypoxia signaling pathway have been performed. The role of HIF stabilization during hypoxia has been extended from the induction of a single gene erythropoietin to the upregulation of a couple of hundred downstream targets, which demonstrates the complexity and importance of the HIF signaling pathway. Accordingly, HIF and its downstream targets are emerging as novel therapeutic options to treat various organ injuries. In this review, we discuss the current understanding of HIF signaling in four different organ systems, including the heart, lung, liver, and kidney. We also discuss the divergent roles of HIF in acute and chronic disease conditions and their revealed functions. Finally, we introduce some of the efforts that are being performed to translate our current knowledge in hypoxia signaling to clinical medicine.
Low oxygen: Protein signalling in human disease A protein family that plays diverse roles in acute and chronic hypoxia (low oxygen) may prove valuable in developing novel therapies for different diseases. Hypoxia, the short- or long-term depletion of oxygen in cells, tissues and organs, is involved in many disease conditions. Holger Eltzschig at the McGovern Medical School in Houston, USA, and co-workers reviewed research into the roles of a key hypoxia regulator, the hypoxia-inducible factor (HIF) protein group, in diseases affecting the heart, lung, liver and kidneys. HIF protein activity is often beneficial in acute conditions such as myocardial ischemia, sending signals to protect cells and increasing tissue tolerance to hypoxia. However, during chronic hypoxia, HIF signaling may contribute to the progression of disease, for example in pulmonary fibrosis. HIF stabilizers and HIF-induced targets as drugs could prove valuable in future treatments.
Databáze: OpenAIRE
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