Renal injury is accelerated by global hypoxia-inducible factor 1 alpha deficiency in a mouse model of STZ-induced diabetesReport as inadecuate

Renal injury is accelerated by global hypoxia-inducible factor 1 alpha deficiency in a mouse model of STZ-induced diabetes - Download this document for free, or read online. Document in PDF available to download.

BMC Endocrine Disorders

, 17:48

Diabetes and Metabolism


BackgroundHypoxia inducible factor 1 HIF-1 activates protective pathways to counteract hypoxia and prevent tissue damage in conjunction with renal injury. The aim of this study was to evaluate a role of HIF-1 in diabetes-induced kidney damage.

MethodsWe used a streptozotocin-induced diabetes mouse model and compared biochemical, histological and molecular parameters associated with kidney damage in Hif1α deficient Hif1α and wild-type mice.

ResultsWe showed that Hif1α deficiency accelerated pathological changes in the early stage of DN. Six weeks after diabetes-induction, Hif1α deficient mice showed more prominent changes in biochemical serum parameters associated with glomerular injury, increased expression of podocyte damage markers, and loss of podocytes compared to wild-type mice. These results indicate that Hif1α deficiency specifically affects podocyte survival in the early phase of DN, resulting in diabetic glomerular injury. In contrast, renal fibrosis was not affected by the global reduction of Hif1α, at least not in the early phase of diabetic exposure.

ConclusionsTogether our data reveal that HIF-1 has an essential role in the early response to prevent diabetes-induced tissue damage and that impaired HIF-1 signaling results in a faster progression of DN. Although the modulation of HIF-1 activity is a high-priority target for clinical treatments, further study is required to investigate HIF-1 as a potential therapeutic target for the treatment of DN.

KeywordsDiabetic complications Diabetic nephropathy Hypoxia Podocyte Mouse model AbbreviationsAdmAdrenomedullin

AGEAdvanced glycation end products

CtgfConnective tissue growth factor

Cx43Connexin 43

DNDiabetic nephropathy

Fn1Fibronectin 1

GSISGlucose-stimulated insulin secretion

HIF-1Hypoxia inducible factor 1



PASPeriodic acid–Schiff staining

Pdk1Pyruvatdehydrogenase kinase1

ROSReactive oxygen species

Sox9SRY Sex Determining Region Y-Box 9


Tgfβ1Transforming growth factor beta 1

VegfaVascular endothelial growth factor


Wt1Wilms tumor 1 homolog

α-SMAAlpha 2 smooth muscle actin

Electronic supplementary materialThe online version of this article doi:10.1186-s12902-017-0200-8 contains supplementary material, which is available to authorized users.

Download fulltext PDF

Author: Romana Bohuslavova - Radka Cerychova - Katerina Nepomucka - Gabriela Pavlinkova


Related documents