HIF-1α: A potential therapeutic opportunity in renal fibrosis

Renal fibrosis is a common outcome of various renal injuries, leading to structural destruction and functional decline of the kidney, and is also a critical prognostic indicator and determinant in renal diseases therapy. Hypoxia is induced in different stress and injuries in kidney, and the hypoxia inducible factors (HIFs) are activated in the context of hypoxia in response and regulation the hypoxia in time. Under stress and hypoxia conditions, HIF-1α increases rapidly and regulates intracellular energy metabolism, cell proliferation, apoptosis, and inflammation. Through reprogramming cellular metabolism, HIF-1α can directly or indirectly induce abnormal accumulation of metabolites, changes in cellular epigenetic modifications, and activation of fibrotic signals. HIF-1α protein expression and activity are regulated by various posttranslational modifications. The drugs targeting HIF-1α can regulate the downstream cascade signals by inhibiting HIF-1α activity or promoting its degradation. As the renal fibrosis is affected by renal diseases, different diseases may trigger different mechanisms which will affect the therapy effect. Therefore, comprehensive analysis of the role and contribution of HIF-1α in occurrence and progression of renal fibrosis, and determination the appropriate intervention time of HIF-1α in the process of renal fibrosis are important ideas to explore effective treatment strategies. This study reviews the regulation of HIF-1α and its mediated complex cascade reactions in renal fibrosis, and lists some drugs targeting HIF-1α that used in preclinical studies, to provide new insight for the study of the renal fibrosis mechanism.