Open AccessRole of Endothelial Prolyl-4-Hydroxylase Domain Protein/Hypoxia-Inducible Factor Axis in Acute Kidney Injury
Author(s) -
Ratnakar Tiwari,
Pinelopi P. Kapitsinou
Publication year - 2021
Publication title -
the nephron journals/nephron journals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.951
H-Index - 72
eISSN - 2235-3186
pISSN - 1660-8151
DOI - 10.1159/000518632
Subject(s) - medicine , hypoxia (environmental) , acute kidney injury , kidney , vascular endothelial growth factor , hypoxia inducible factors , ischemia , angiogenesis , endothelial stem cell , kidney transplantation , endocrinology , pathology , biology , chemistry , biochemistry , organic chemistry , oxygen , in vitro , vegf receptors , gene
Ischemia reperfusion injury (IRI) results from a cessation or restriction of blood supply to an organ followed by reestablishment of perfusion and reoxygenation. In the kidney, IRI due to transplantation, cardiac surgery with cardiopulmonary bypass, and other major vascular surgeries contributes to acute kidney injury (AKI), a clinical condition associated with significant morbidity and mortality in hospitalized patients. In the postischemic kidney, endothelial damage promotes inflammatory responses and leads to persistent hypoxia of the renal tubular epithelium. Like other cell types, endothelial cells respond to low oxygen tension by multiple hypoxic signaling mechanisms. Key mediators of adaptation to hypoxia are hypoxia-inducible factors (HIF)-1 and -2, transcription factors whose activity is negatively regulated by prolyl-hydroxylase domain proteins 1 to 3 (PHD1 to PHD3). The PHD/HIF axis controls several processes determining injury outcome, including ATP generation, cell survival, proliferation, and angiogenesis. Here, we discuss recent advances in our understanding of the endothelial-derived PHD/HIF signaling and its effects on postischemic AKI.