TGF-beta promotes expression of fibrosis-related genes through the induction of histone variant H3.3 and histone chaperone HIRA
| Project/Area Number |
16K19489
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Kidney internal medicine
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| Research Institution | Hiroshima University |
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Principal Investigator |
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| Research Collaborator |
MASAKI Takao 広島大学, 病院(医), 教授 (30397913)
DOI Shigehiro 広島大学, 病院(医), 助教 (80626127)
NAKASHIMA Ayumu 広島大学, 医歯薬保健学研究科(医), 共同研究講座教授 (40448262)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | CKD / ESKD / 腎線維化 / ヒストンバリアント / H3.3 / ヒストンシャペロン / HIRA / エピジェネティクス / エピジェネティック |
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| Outline of Final Research Achievements |
Renal fibrosis is a histological manifestation that occurs in almost every type of chronic kidney disease. Histone variant H3.3 and its chaperone, HIRA, serve as epigenetic marks that regulate transcriptional activity. In this study, we assessed the roles of histone H3.3 and HIRA in TGF-β1-induced renal fibrosis. In UUO mice, the levels of histone H3.3 and HIRA were upregulated in the kidneys via a Smad3-dependent pathway, and decreased by a TGF-β1 neutralizing antibody. Additionally, knockdown of HIRA decreased H3.3 and fibrogenesis. ChIP analysis revealed that promoters of fibrosis-related genes were immunoprecipitated with both HIRA and histone H3.3. Lastly, in human kidney biopsies, HIRA and H3.3 immunostaining correlated positively with areas of fibrosis. In conclusion, inhibition of the TGF-β1-induced histone chaperone, HIRA, via histone H3.3 induction, regulated the expression of fibrosis-related genes, and HIRA is a candidate therapeutic target for chronic kidney disease.
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Report
(3 results)
Research Products
(2 results)
