Association of p38 MAPK with natriuretic peptide receptors in renal glomeruli
| Project/Area Number |
21K16188
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53040:Nephrology-related
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2021-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2022: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | ポドサイト / ナトリウム利尿ペプチド / p38 MAPK / ANP / 内皮障害 / ハンプ / p38 |
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| Outline of Research at the Start |
本申請研究は、ポドサイト特異的ナトリウム利尿ペプチド受容体A(GC-A)&p38 MAPKノックアウトマウスで認められた糸球体障害、内皮障害、糸球体係蹄内血栓形成傾向に全身性のp38 MAPKがどのように関わるのかを検討する。また、培養ポドサイトのp38 MAPKとGC-AをCRISPR/Cas9系でノックアウトした細胞を作出し、内皮細胞との共培養系を用いて、網羅的解析から得られた遺伝子群であるⅧ因子、ⅩⅢ因子とPAI-1を中心にノックアウトポドサイトと内皮細胞における発現変化と機能的意義を解明する。
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| Outline of Final Research Achievements |
This study focused on the functions of natriuretic peptide (Guanylyl cyclase-A; GC-A) and p38 MAPK in glomerular podocytes. Podocyte-specific GC-A & p38 MAPK double knockout mice showed podocyte damage and thrombi in the glomerular coxae.
Next, when GC-A expression was decreased in p38 MAPK knockout cultured podocytes, the expression of inflammatory cytokines elevated. Moreover, it also increased the expression of TGF-β and FN in co-cultured human umbilical vein endothelial cells.
These results suggest that deletion at p38 MAPK and GC-A in podocytes causes damage in podocytes and vascular endothelial cells.
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| Academic Significance and Societal Importance of the Research Achievements |
今回の研究により、p38 MAPKが糸球体のポドサイトと血管の血管内皮細胞のそれぞれとの関連性において非常に重要なタンパク質であることが明らかになった。また、これまでヒト培養ポドサイトにおいてゲノム編集技術の応用が成功した例は少なく、本技術がポドサイトに応用可能であることがわかり、今後の研究の発展性を大きく広げた。
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Report
(2 results)
Research Products
(9 results)
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[Journal Article] Intestinal Bacterial Translocation Contributes to Diabetic Kidney Disease.2022
Author(s)
Linh HT, Iwata Y, Senda Y, Sakai-Takemori Y, Nakade Y, Oshima M, Nakagawa-Yoneda S, Ogura H, Sato K, Minami T, Kitajima S, Toyama T, Yamamura Y, Miyagawa T, Hara A, Shimizu M, Furuichi K, Sakai N, Yamada H, Asanuma K, Matsushima K, Wada T.
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Journal Title
J Am Soc Nephrol.
Volume: -
Issue: 6
Pages: 1105-1119
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Suppressor of cytokine signalling 3 (SOCS3) expressed in podocytes attenuates glomerulonephritis and suppresses autoantibody production in an imiquimod-induced lupus model2021
Author(s)
Fukuta M, Suzuki K, Kojima S, Yabe Y, Suzuki K, Iida K, Yamada H, Makino S, Iwata A, Tanaka S, Iwamoto T, Suto A, Nakagomi D, Wakashin H, Maezawa Y, Maezawa Y, Takemoto M, Asanuma K, Nakajima H.
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Journal Title
Lupus Sci Med.
Volume: 8
Issue: 1
Pages: 426-426
DOI
Related Report
Peer Reviewed / Open Access
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