title: Perspective in chronic kidney disease: targeting hypoxia-inducible factor (HIF) as potential therapeutic approach.
abstract: Tissue hypoxia is a pathologic feature of many human diseases like cancer, myocardial infarction, stroke, and kidney disease. Convincing data from clinical studies in patients with chronic renal failure point to chronic hypoxia of kidneys as the end result of multiple processes and mechanisms. In acute as well as chronic diseases, tissue hypoxia not only implies a risk of energy deprivation but also induces regulatory mechanisms with profound influence on gene expression. Moreover, once established, accumulating evidence points to this chronic hypoxia as the central player along with final common pathway to end-stage renal disease (ESRD). An evolutionarily preserved oxygen-sensing mechanism enables cells to adapt and maintain homeostasis under hypoxic conditions by transcriptional activation of a host of genes mediating metabolic adaptation, angiogenesis, energy conservation, erythropoiesis, in addition to cell survival. The endogenous oxygen-sensing mechanism incorporates hypoxia-inducible factors (HIFs) that hub cellular response to hypoxia and comprises a family of oxygen-sensitive basic helix-loop-helix proteins that control the cellular transcriptional response to hypoxia. Hypoxia-inducible factor 1 (HIF-1) is thus a significant mediator of physiological responses to acute and chronic hypoxia. Since HIF is activated to suboptimal levels in pathogenic renal states, therapeutic activation holds a promising novel and effective approach to the treatment of ESRD. Current insights into the regulation of HIF may augment the understanding of the role of hypoxia in renal failure progression and may unbolt new options to improve hypoxia tolerance and induce nephroprotection.
authors.affiliation: Department of Pharmacology, Shankersinh Vaghela Bapu Institute of Pharmacy, Unava, Gujarat, India. aaishwarya.22@gmail.com
authors.forename: Aaishwarya B
authors.initials: AB
authors.lastname: Deshmukh
authors.forename: Jayvadan K
authors.initials: JK
authors.lastname: Patel
authors.forename: Ashish R
authors.initials: AR
authors.lastname: Prajapati
authors.forename: Shreya
authors.initials: S
authors.lastname: Shah
mesh_terms: D000818:Animals; D018450:Disease Progression; D005786:Gene Expression Regulation; D006801:Humans; D000860:Hypoxia / Q000150:complications / Q000235:genetics / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis* / Q000235:genetics; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000378:metabolism* / Q000628:therapy; D018384:Oxidative Stress
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit