Aberrant post-translational modification in diabetic nephropathy
| Project/Area Number |
17K16097
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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 | Teikyo University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 糖尿病性腎症 / KLHL3 / リン酸化 / 脱リン酸化 / 糖尿病 / 高血圧 |
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| Outline of Final Research Achievements |
In this study, we focused on the post-translational modification of ubiquitin ligase component Kelch-like 3 (KLHL3), a novel effector of angiotensin II, and analyzed its association with diabetic nephropathy. Phosphorylation of KLHL3 was increased in the kidney of db / db mice. Renal PKC was also increased,and PKC inhibitor suppressed KLHL3 phosphorylation in vitro and in vivo. We also found that an SGLT2 inhibitor ipragliflozin ameliorated the dysregulation of KLHL3. Moreover, in an effort to dissect the mechanisms that regulate KLHL3 phosphorylation, we found that Ser/Thr phosphatase calcineurin dephosphorylates KLHL3.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究はKLHL3のリン酸化の病的意義を解明を目指すものであるが、糖尿病性腎症におけるKLHL3のリン酸化異常を突き止めたことで、病態の分子基盤の一部が解明されることとなり、臨床的有用性が高い。
また、CalcineurinがKLHL3-S433を脱リン酸化することを見出したが、Calcineurin阻害薬（CNI）は免疫抑制薬として臨床で頻用されている。CalcineurinがKLHL3の脱リン酸化酵素として働くことは重要な結果であるが、CNIによる高血圧の病態の一部を解明したことは、臨床的にも重要と考えられる。
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Report
(3 results)
Research Products
(4 results)
