Involvement of acidification of glomerular cells by AGE-cholesterol-aggregated proteins in development of diabetic nephropathy
| Project/Area Number |
26460635
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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 | Meijo University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
水野 智博 名城大学, 薬学部, 助教 (40711669)
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| Co-Investigator(Renkei-kenkyūsha) |
TAKAHASHI Kazuo 藤田保健衛生大学, 医学部, 講師 (90631391)
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| Research Collaborator |
YAMADA Shigeki
HAYASHI Takahiro
HIRASAWA Yasushi
FENG Yibin
AKIYAMA Shinichi
YUZAWA Yukio
UCHIYA Keiichi
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 糖尿病性腎症 / 糖化凝集タンパク質 / コレステロール / アポトーシス / メサンギウム細胞 / スタウロスポリン / アクチンフィラメント / 最終糖化産物 / 凝集タンパク質 / アクアポリン / 酸性化 / 細胞内ｐH / サイトカイン / 炎症 / 細胞内pH / 酸性溶液 |
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| Outline of Final Research Achievements |
We have demonstrated the validity of our hypothesis regarding the development of diabetic nephropathy, which was as follows: AGE-cholesterol-aggregated albumin (ACAA) is formed in the blood flow of diabetic patients, and taken up in glomerular mesangial cells to achieve the breakdown of ACAA in lysosome. Simultaneously, mitochondria of mesangial cells are activated, and mesangial cells are acidified followed by an increase in pro-inflammatory cytokine expression. The cytokines induce inflammation in the glomeruli repeatedly, resulting in diabetic nephropathy. We also clarified the mechanisms for protecting mesangial cells from acidification due to ACAA or an acidic environment. Additionally, our results suggested that ACAA causes damage in mesangial mitochondria followed by apoptosis.
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Report
(4 results)
Research Products
(36 results)
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[Journal Article] Complement component 5 promotes lethal thrombosis2017
Author(s)
Tomohiro Mizuno, Kengo Yoshioka, Masashi Mizuno, Mie Shimizu, Fumihiko Nagano, Tomoyuki Okuda, Naotake Tsuboi, Shoichi Maruyama, Tadashi Nagamatsu, Masaki Imai
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Journal Title
Complement component 5 promotes lethal thrombosis.
Volume: 16
Issue: 1
Pages: 42714-42714
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The Level of IgA Antibodies to Endothelial Cells Correlates with Histological Evidence of Disease Activity in Patients with Lupus Nephritis.2016
Author(s)
Kondo A, Takahashi K, Mizuno T, Kato A, Hirano D, Yamamoto N, Hayashi H, Koide S, Takahashi H, Hasegawa M, Hiki Y, Yoshida S, Miura K, Yuzawa Y.
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Journal Title
PLoS One
Volume: 11
Issue: 10
Pages: e0163085-e0163085
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Complement promote releasing transglutaminase 2 from cytoplasm.2016
Author(s)
Kaori Hara, Tomohiro Mizuno, Kazuo Takahashi, Masashi Mizuno, Akihiro Kato, Takanori Onouchi, Yutaka Tsutsumi, Hideki Tatsukawa, Tadashi Nagamatsu, Kiyotaka Hitomi, Yukio Yuzawa
Organizer
XXVI International Complement Workshop
Place of Presentation
金沢
Year and Date
2016-09-05
Related Report
Invited
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