Molecular mechanisms of nephrotic syndrome induced by cytoskeletal protein abnormalities
Project/Area Number |
18K07830
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 52050:Embryonic medicine and pediatrics-related
|
Research Institution | Tokyo Women's Medical University |
Principal Investigator |
|
Co-Investigator(Kenkyū-buntansha) |
安彦 行人 国立医薬品食品衛生研究所, 毒性部, 主任研究官 (40370944)
栗原 秀剛 藍野大学, 医療保健学部, 教授 (80311976)
|
Project Period (FY) |
2018-04-01 – 2021-03-31
|
Project Status |
Completed (Fiscal Year 2020)
|
Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | 巣状分節性糸球体硬化症 / ネフローゼ症候群 / Epstein症候群 / 遺伝子解析 / 細胞骨格蛋白 / ポドサイト / MYH9 / 細胞骨格 / ノックインマウス |
Outline of Final Research Achievements |
Myosin-IIA is a cytoskeletal protein encoded by the MYH9 gene, and is expressed in glomerular podocytes and endothelial cells. Mutations in the MYH9 gene cause Epstein syndrome and focal segmental glomerulosclerosis in the kidney. We analyzed kidney-specific MYH9 knock-in mice, which confirmed proteinuria at 13 weeks induced by tamoxifen treatment at 4 weeks after birth. Additionally, we analyzed genotype-phenotype correlation in Epstein syndrome, which showed a significant impact of mutations in the head domain on renal prognosis. Pathological examinations of kidney biopsy specimens showed endothelial injury.
|
Academic Significance and Societal Importance of the Research Achievements |
難治性ネフローゼ症候群は高度蛋白尿、腎組織の巣状糸球体硬化症(FSGS)、末期腎不全を来す疾患であり、その病態解明は小児腎疾患診療において最大課題の一つである。細胞骨格蛋白であるミオシン重鎖myosin-IIA(MYH9遺伝子がコードする蛋白)は糸球体上皮細胞(ポドサイト)に発現しており、その異常はEpstein症候群を起こし、腎組織はFSGSを呈する。今回の腎臓特異的MYH9変異ノックインマウスの解析とヒトEpstein症候群の腎病理像の解析はFSGSの病態解明につながり、遺伝子変異によらない特発性FSGSの病態理解の一助となりうる。
|
Report
(4 results)
Research Products
(37 results)
-
-
-
-
-
[Journal Article] Individualized concept for the treatment of autosomal recessive polycystic kidney disease with end-stage renal disease.2020
Author(s)
Miura K, Sato Y, Yabuuchi T, Kaneko N, Ishizuka K, Chikamoto H, Akioka Y, Nawashiro Y, Hisano M, Imamura H, Miyai T, Sakamoto S, Kasahara M, Fuchinoue S, Okumi M, Ishida H, Tanabe K, Hattori M.
-
Journal Title
Pediatr Nephrol
Volume: Mar 3
Issue: 3
DOI
Related Report
Peer Reviewed / Int'l Joint Research
-
-
-
-
-
-
-
[Journal Article] Renal hypoplasia can be the cause of membranous nephropathy-like lesions.2020
Author(s)
Keiichi Takizawa, Kenichiro Miura, Naoto Kaneko, Tomoo Yabuuchi, Kiyonobu Ishizuka, Shoichiro Kanda, Yutaka Harita, Yuko Akioka, Shigeru Horita, Sekiko Taneda, Kazuho Honda, Motoshi Hattori
-
Journal Title
Clin Exp Nephrol
Volume: 24
Issue: 9
Pages: 813-820
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Rapid progression to end-stage renal disease in a child with IgA-dominant infection-related glomerulonephritis associated with parvovirus B19.2020
Author(s)
Yoko Shirai, Kenichiro Miura, Tomoo Yabuuchi, Takeshi Nagasawa, Kiyonobu Ishizuka, Kazuhiro Takahashi, Sekiko Taneda, Kazuho Honda, Yutaka Yamaguchi, Hitoshi Suzuki, Yusuke Suzuki, Motoshi Hattori
-
Journal Title
CEN Case Rep
Volume: 9
Issue: 4
Pages: 423-430
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
-
-
[Journal Article] Organoids from nephrotic disease-derived iPSCs identify impaired NEPHRIN localization and slit diaphragm formation in kidney podocytes.2018
Author(s)
Tanigawa S, Islam M, Naganuma H, Yoshimura Y, Miike K, Sharmin S, Haque F, Era T, Nakazato H, Nakanishi K, Sakuma T, Yamamoto T, Kurihara H, Taguchi A, Nishinakamura R
-
Journal Title
Stem Cell Rep
Volume: 11
Issue: 3
Pages: 1-14
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Presentation] Response to steroid and immunosuppressive therapies may predict post-transplant recurrence of focal segmental glomerulosclerosis.2021
Author(s)
Miura K, Ando T, Kanda S, Hashimoto T, Kaneko N, Ishizuka K, Hamada R, Hataya H, Hotta K, Gotoh Y, Nishiyama K, Hamasaki Y, Shishido S, Fujita N, Hattori M.
Organizer
14th Asian Congress of Pediatric Nephrology
Related Report
Int'l Joint Research
-
[Presentation] Long-term renal prognosis of Lowe syndrome.2020
Author(s)
Miura K, Yabuuchi T, Ishiwa S, Harita Y, Ishizuka K, Kanda S, Sato A, Isojima T, Hamada R, Ishikura K, Igarashi T, Hattori M.
Organizer
18th Asian Pacific Congress of Nephrology
Related Report
Int'l Joint Research
-
-
-
-
-
-
[Presentation] The size of urinary podocyte in focal segmental glomerulosclerosis2018
Author(s)
Shirai Y, Miura K, Yokoyama T, Horita S, Iida T, Taniguchi Y, Nagasawa T, Ban H, Yabuuchi T, Kaneko N, Takagi Y, Ishizuka K, Hara M, Hattori M
Organizer
American Society of Nephrology Kidney Week 2018
Related Report
Int'l Joint Research
-
-
-
-
-
-