2013 Fiscal Year Final Research Report
a role of HIF-3 in adjusting cellular hypoxia response and its implications in progressive renal disease
| Project/Area Number |
22790781
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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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) |
2010-04-01 – 2014-03-31
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| Keywords | HIF-3 / 進行性腎疾患 |
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| Research Abstract |
In this study, we investigated a role of hypoxia-inducible factor (HIF)-3 as a regulator of cellular hypoxia response by HIF-1. HIF-3alpha mRNA was transcriptionally up-regulated by hypoxia in a HIF-1- dependent manner. Promoter analysis revealed that HIF-3alpha is a novel HIF-1 target gene. Overexpression of HIF-3alpha in a human proximal tubular cell line, HK-2, reduced the hypoxic induction of lysyl-oxidase most significantly among other known HIF targets. Functionally, HIF-3 counteracted the disappearance of epithelial markers, such as E-cadherin, by hypoxia and inhibited the acquisition of cell migration. In immunohistochemistry, the expression of HIF-3alpha was most evident in the nuclei of tubular epithelial cells in various models of CKD representing fibrosis. In summary, results of the present study clarify the importance of HIF-3 in counteracting kidney fibrosis in the hypoxic environment.
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[Journal Article] Sperm-associated antigen 4, a novel hypoxia-inducible factor 1 target, regulates cytokinesis, and its expression correlates with the prognosis of renal cell carcinoma2013
Author(s)
Shoji K, Murayama T, Mimura I, Wada T, Kume H, Goto A, Ohse T, Tanaka T, Inagi R, van der Hoorn FA, Manabe I, Homma Y, Fukayama M, Sakurai T, Hasegawa T, Aburatani H, Kodama T, Nangaku M
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Journal Title
Am J Pathol.
Volume: 182(6)
Pages: 2191-203
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