{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kapitsinou PP"],"funding":["NIDDK NIH HHS"],"pagination":["2396-409"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4092875"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["124(6)"],"pubmed_abstract":["The hypoxia-inducible transcription factors HIF-1 and HIF-2 mediate key cellular adaptions to hypoxia and contribute to renal homeostasis and pathophysiology; however, little is known about the cell type-specific functions of HIF-1 and HIF-2 in response to ischemic kidney injury. Here, we used a genetic approach to specifically dissect the roles of endothelial HIF-1 and HIF-2 in murine models of hypoxic kidney injury induced by ischemia reperfusion or ureteral obstruction. In both models, inactivation of endothelial HIF increased injury-associated renal inflammation and fibrosis. Specifically, inactivation of endothelial HIF-2α, but not endothelial HIF-1α, resulted in increased expression of renal injury markers and inflammatory cell infiltration in the postischemic kidney, which was reversed by blockade of vascular cell adhesion molecule-1 (VCAM1) and very late antigen-4 (VLA4) using monoclonal antibodies. In contrast, pharmacologic or genetic activation of HIF via HIF prolyl-hydroxylase inhibition protected wild-type animals from ischemic kidney injury and inflammation; however, these same protective effects were not observed in HIF prolyl-hydroxylase inhibitor-treated animals lacking endothelial HIF-2. Taken together, our data indicate that endothelial HIF-2 protects from hypoxia-induced renal damage and represents a potential therapeutic target for renoprotection and prevention of fibrosis following acute ischemic injury."],"journal":["The Journal of clinical investigation"],"pubmed_title":["Endothelial HIF-2 mediates protection and recovery from ischemic kidney injury."],"pmcid":["PMC4092875"],"funding_grant_id":["P30 DK020593","P30-DK079312","R01-DK007124","R01 DK077124","R01 DK099345","R01-DK081646","P30-DK07934","P30 DK079312","P30 DK079341","R01 DK081646"],"pubmed_authors":["Bian A","Sutton TA","Haase VH","Erickson-Miller CL","Kobayashi H","Michael M","Harris RC","Davidoff O","Zhang MZ","Kapitsinou PP","Yao B","Sano H","Duffy KJ"],"additional_accession":[]},"is_claimable":false,"name":"Endothelial HIF-2 mediates protection and recovery from ischemic kidney injury.","description":"The hypoxia-inducible transcription factors HIF-1 and HIF-2 mediate key cellular adaptions to hypoxia and contribute to renal homeostasis and pathophysiology; however, little is known about the cell type-specific functions of HIF-1 and HIF-2 in response to ischemic kidney injury. Here, we used a genetic approach to specifically dissect the roles of endothelial HIF-1 and HIF-2 in murine models of hypoxic kidney injury induced by ischemia reperfusion or ureteral obstruction. In both models, inactivation of endothelial HIF increased injury-associated renal inflammation and fibrosis. Specifically, inactivation of endothelial HIF-2α, but not endothelial HIF-1α, resulted in increased expression of renal injury markers and inflammatory cell infiltration in the postischemic kidney, which was reversed by blockade of vascular cell adhesion molecule-1 (VCAM1) and very late antigen-4 (VLA4) using monoclonal antibodies. In contrast, pharmacologic or genetic activation of HIF via HIF prolyl-hydroxylase inhibition protected wild-type animals from ischemic kidney injury and inflammation; however, these same protective effects were not observed in HIF prolyl-hydroxylase inhibitor-treated animals lacking endothelial HIF-2. Taken together, our data indicate that endothelial HIF-2 protects from hypoxia-induced renal damage and represents a potential therapeutic target for renoprotection and prevention of fibrosis following acute ischemic injury.","dates":{"release":"2014-01-01T00:00:00Z","publication":"2014 Jun","modification":"2025-04-26T09:13:59.876Z","creation":"2019-03-27T01:31:53Z"},"accession":"S-EPMC4092875","cross_references":{"pubmed":["24789906"],"doi":["10.1172/jci69073","10.1172/JCI69073"]}}