Angiogenesis in renal fibrosis
| Project/Area Number |
17K08958
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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 |
Applied pharmacology
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| Research Institution | Osaka City University |
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Principal Investigator |
Miura Katsuyuki 大阪市立大学, 大学院医学研究科, 名誉教授 (00183624)
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| Co-Investigator(Kenkyū-buntansha) |
冨田 修平 大阪市立大学, 大学院医学研究科, 教授 (00263898)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 腎線維化 / 低酸素 / 低酸素誘導因子 / HIF-PHD阻害薬 / 血管新生 / PAI-1 / CTGF / 血管内皮増殖因子 / 線維化 / UUOモデル / HIF / PHD阻害剤 / CKD |
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| Outline of Final Research Achievements |
Hypoxia inducible factors (HIFs) are transcription factors that mediate cellular adaptation to hypoxia by regulating gene expression of glycolytic enzymes, angiogenesis and hematopoiesis. Present study was conducted to examine the role of HIF in renal fibrogenesis and also to test if HIF-dependent VEGF expression is involved in the mechanism. Although HIF stabilizer stimulated VEGF gene expression in the intact kidney, neither HIF-1 gene ablation nor HIF stabilizer affected VEGF expression in the fibrotic kidney, thus we failed to demonstrate the role of HIF-dependent VEGF expression in attenuating renal fibrosis. Even though HIF-1 gene ablation or HIF stabilizer did not affect renal fibrosis, HIF-dependent acceleration of gene expression of profibrogenic molecules, PAI-1 and CTGF can be seen transiently. It is suggested that HIF-dependent profibrogenic mechanisms are operating at the early onset of renal fibrosis but its contribution declines with the progression of renal fibrosis.
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| Academic Significance and Societal Importance of the Research Achievements |
末期腎不全では腎の線維化に伴い造血因子エリスロポエチン産生が低下し、腎性貧血が生じるため、エリスロポエチン製剤の注射が必要となる。このエリスロポエチン産生には転写因子の低酸素誘導因子HIFが必要で、このHIF安定剤が腎性貧血の治療薬として臨床応用されるようになった。HIFは腎線維化がその成因に深く関わる可能性がある。今回の研究は腎線維化におけるHIFの働きについて、特に血管新生と関連するかについて検討した。腎線維化でのHIFと関連した血管新生の役割は解明できなかったが、HIFに関連した線維化関連分子の役割を示すことが出来た。この結果はHIF安定剤の腎性貧血の臨床適応において貴重な情報となる。
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Report
(4 results)
Research Products
(13 results)
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[Presentation] The role of HIF-1 in the development of renal fibrosis in mouse UUO model with special reference to HIF-1 dependent gene expression.2018
Author(s)
Kabei K., Osada-Oka M., Nozaki M., Shiota M., Tanaka, M., Tomita S. and Miura K.
Organizer
18th World Congress of Basic and Clinical Pharmacology, July1-6, 2018, Kyoto, Japan
Related Report
Int'l Joint Research
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