2018 Fiscal Year Final Research Report
The role of proteolysis in podocyte and mechanisms of CKD along with aging
| Project/Area Number |
17K19653
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
General internal medicine and related fields
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| Research Institution | Chiba University |
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Principal Investigator |
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| Project Period (FY) |
2017-06-30 – 2019-03-31
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| Keywords | ポドサイト / 蛋白分解 / 老化 / ユビキチン / プロテアソーム |
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| Outline of Final Research Achievements |
Podocyte plays an important role in glomerular filtration in kidney. Podocyte injury causes the progression of chronic kidney disease (CKD).
We considered dysfunction of proteolysis in podocyte causes the progression of CKD with aging. We generated podocyte-specific dysfunctional mice of the ubiquitin-proteasome system (UPS), which is one of the intracelluar protein degradation systems. The mice showed podocyte injury and progression of CKD in young age. Senescence promotion and apoptosis were observed in podocyte of the mice. In vitro study, anti-oxidant and autophgy activation suppressed the apoptosis of podocyte. This suggested that these reagents could suppress the aging of podocytes and the progeression of CKD due to UPS dysfunction.
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| Free Research Field |
腎臓内科学
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| Academic Significance and Societal Importance of the Research Achievements |
慢性腎不全(CKD)の患者数は、高齢化が進むにつれて増加し、CKDの進行抑制薬の開発が望まれる。加齢により機能が低下するポドサイトの蛋白分解機能が、ポドサイト障害を引き起こしてCKDの原因となりうることを示し、またCKDの進行を抑制する可能性のある薬剤候補を示すことができた。これは、UPSを治療ターゲットとした、CKDの進行抑制薬の開発にエビデンスを与える。学術的には、ポドサイト特異的なUPSの機能不全マウスの解析を初めて行うことで、ポドサイトにおけるUPSの重要性を示すことができた。
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