2016 Fiscal Year Final Research Report
Regulation of hypoxia inducible genes in chronic kidney disease
| Project/Area Number |
26461215
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | 慢性腎臓病 / 低酸素 |
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| Outline of Final Research Achievements |
Tubulointerstitial hypoxia is a final common pathway in progressive kidney disease. Hypoxia inducible factors (HIF1 and HIF2) play important roles for the adaptation of intrinsic cells of the kidney. This study aimed to characterize the functional roles of HIF3, a putative suppressor against other HIFs. Among 100-200 HIF target genes, HIF3 selectively suppressed the hypoxic induction of lysyl oxidase(LOX). In vivo, pharmacological inhibition of LOX led to amelioration of interstitial fibrosis in multiple models of CKD, such as unilateral ureteral obstruction and diabetic kidney disease. Results of these studies highlight a novel antifibrotic mechanisms of HIF3, which was mechanistically achieved by the selective inhibition of LOX expression.
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| Free Research Field |
腎臓内科学
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