BMC Endocrine Disorders | |
Renal injury is accelerated by global hypoxia-inducible factor 1 alpha deficiency in a mouse model of STZ-induced diabetes | |
Research Article | |
Katerina Nepomucka1  Gabriela Pavlinkova1  Romana Bohuslavova1  Radka Cerychova2  | |
[1] Laboratory of Molecular Pathogenetics, Institute of Biotechnology CAS, BIOCEV, Center of Excellence, Prumyslova 595, 25242, Vestec, Czechia;Laboratory of Molecular Pathogenetics, Institute of Biotechnology CAS, BIOCEV, Center of Excellence, Prumyslova 595, 25242, Vestec, Czechia;Faculty of Science, Charles University, Prague, Czechia; | |
关键词: Diabetic complications; Diabetic nephropathy; Hypoxia; Podocyte; Mouse model; | |
DOI : 10.1186/s12902-017-0200-8 | |
received in 2017-01-01, accepted in 2017-07-31, 发布年份 2017 | |
来源: Springer | |
【 摘 要 】
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.
【 授权许可】
CC BY
© The Author(s). 2017
【 预 览 】
Files | Size | Format | View |
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RO202311097084476ZK.pdf | 7547KB | download |
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