Investigation of the role of NFAT5 in chronic kidney injury.
Project/Area Number |
18K08247
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 53040:Nephrology-related
|
Research Institution | Kumamoto University |
Principal Investigator |
|
Co-Investigator(Kenkyū-buntansha) |
向山 政志 熊本大学, 大学院生命科学研究部(医), 教授 (40270558)
|
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: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
|
Keywords | 慢性腎臓病 / NFAT5 / 腎尿細管 / 腎線維化 / 尿濃縮 / 慢性腎障害 / 転写因子 / 浸透圧 / 尿細管 |
Outline of Final Research Achievements |
We generated inducible and renal tubular cell-specific NFAT5 knock out mice. The mice exhibited polyuria, high blood pressure, and hypernatremia. The mice were subjected to unilateral ureteral obstruction (UUO), and then the role of renal tubular NFAT5 in renal fibrosis was investigated. The deficit of NFAT5 exacerbated UUO-induced renal fibrosis in KO mice. UUO increased the expression of kidney injury makers and induced apoptosis and migration of macrophage greater in KO mice than in wild type (WT) mice. These results suggest that renal tubular NFAT5 contributes to suppression of renal fibrosis induced by migration of macrophage and inflammation.
|
Academic Significance and Societal Importance of the Research Achievements |
本研究は、我が国では成人人口の13%にあたる患者が存在するとされる慢性腎臓病(CKD)の新規治療法の開発に資するものである。CKDの原因は、腎炎などの腎臓から発症するものだけでなく、高血圧、糖尿病などの生活習慣病、膠原病など多岐に及ぶが、その進行は、腎組織の線維化という共通の過程を経て、末期腎不全に至る。本研究により、腎臓において強い活性を有するNFAT5がCKDにおける腎線維化の進展抑制に寄与することが新たに明らかとなった。また、本研究により、腎臓のNFAT5が食塩摂取により誘発される高血圧においても重要な役割を果たすことが示唆された。新規治療への応用に向けて、さらなる研究の進展が望まれる。
|
Report
(4 results)
Research Products
(43 results)
-
-
-
[Journal Article] Regulation of Rhcg, an ammonia transporter, by aldosterone in the kidney.2021
Author(s)
Eguchi K, Izumi Y, Yasuoka Y, Nakagawa T, Ono M, Maruyama K, Matsuo N, Hiramatsu A, Inoue H, Nakayama Y, Nonoguchi H, Lee HW, Weiner ID, Kakizoe Y, Kuwabara T, Mukoyama M.
-
Journal Title
J Endocrinol.
Volume: in press
Issue: 2
Pages: 95-112
DOI
Related Report
Peer Reviewed / Int'l Joint Research
-
-
-
-
[Journal Article] Erythropoietin production by the kidney and the liver in response to severe hypoxia evaluated by Western blotting with deglycosylation2020
Author(s)
Yukiko Yasuoka, Takashi Fukuyama, Yuichiro Izumi, Yushi Nakayama, Hideki Inoue, Kengo Yanagita, Tomomi Oshima, Taiga Yamazaki, Takayuki Uematsu 2, Noritada Kobayashi 2, Yoshitaka Shimada 5, Yasushi Nagaba, Masashi Mukoyama, Tetsuro Yamashita, Yuichi Sato, Jeff M Sands, Katsumasa Kawahara, Hiroshi Nonoguchi
-
Journal Title
Physiol Rep.
Volume: 12
Issue: 12
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] Suppressed ER-associated degradation by intraglomerular cross talk between mesangial cells and podocytes causes podocyte injury in diabetic kidney disease.2020
Author(s)
Fujimoto D, Kuwabara T, Hata Y, Umemoto S, Kanki T, Nishiguchi Y, Mizumoto T, Hayata M, Kakizoe Y, Izumi Y, Takahashi S, Mukoyama M.
-
Journal Title
FASEB J
Volume: 34
Issue: 11
Pages: 854-860
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Differentiation of endogenous erythropoietin and exogenous ESAs by Western blotting.2020
Author(s)
Yasuoka Y, Fukuyama T, Izumi Y, Yamashita T, Nakayama Y, Inoue H, Yanagita K, Oshima T, Yamazaki T, Uematsu T, Kobayashi N, Shimada Y, Nagaba Y, Mukoyama M, Sato Y, Sands JM, Kawahara K, Nonoguchi H.
-
Journal Title
Heliyon.
Volume: 6
Issue: 11
Pages: e05389-e05389
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] Circulating angiopoietin-like protein 2 levels and arterial stiffness in patients receiving maintenance hemodialysis: A cross-sectional study.2020
Author(s)
Fukami H, Morinaga J, Okadome Y, Nishiguchi Y, Iwata Y, Kanki T, Nakagawa T, Izumi Y, Kakizoe Y, Kuwabara T, Horiguchi H, Sato M, Kadomatsu T, Miyata K, Tajiri T, Oike Y, Mukoyama M.
-
Journal Title
Atherosclerosis.
Volume: 315
Pages: 18-23
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
[Journal Article] Insufficiency of urinary acid excretion of overweight or obese patients with chronic kidney disease and its involvement with renal tubular injury.2019
Author(s)
Eguchi K, Izumi Y, Nakayama Y, Inoue H, Marume T, Matsuo N, Hiramatsu A, Ono M, Kakizoe Y, Kuwabara T, Nonoguchi H, Mukoyama M.
-
Journal Title
Nephrology
Volume: 24
Issue: 11
Pages: 1131-1141
DOI
Related Report
Peer Reviewed
-
-
[Journal Article] Autosomal dominant Alport syndrome due to a COL4A4 mutation with an additional ESPN variant detected by whole-exome analysis2019
Author(s)
Izumi Yuichiro, Hamaguchi Ami, Miura Rei, Nakagawa Terumasa, Nakagawa Miyuki, Saida Ken, Miyake Noriko, Nagayoshi Yu, Kakizoe Yutaka, Miyoshi Taku, Kohda Yukimasa, Misumi Yohei, Matsumoto Naomichi, Ando Yukio, Mukoyama Masashi.
-
Journal Title
CEN Case Reports
Volume: 9
Issue: 1
Pages: 59-64
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Circulating angiopoietin-like protein 2 levels and mortality risk in patients receiving maintenance hemodialysis: a prospective cohort study2019
Author(s)
Morinaga J, Kakuma T, Fukami H, Hayata M, Uchimura K, Mizumoto T, Kakizoe Y, Miyoshi T, Shiraishi N, Adachi M, Izumi Y, Kuwabara T, Okadome Y, Sato M, Horiguchi H, Sugizaki T, Kadomatsu T, Miyata K, Tajiri S, Tajiri T, Tomita K, Kitamura K, Oike Y, Mukoyama M.
-
Journal Title
Nephrology Dialysis Transplantation
Volume: 印刷中
Issue: 5
Pages: 854-860
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Doxycycline attenuates cisplatin-induced acute kidney injury through pleiotropic effects2018
Author(s)
Nakagawa T, Kakizoe Y, Iwata Y, Miyasato Y, Mizumoto T, Adachi M, Izumi Y, Kuwabara T, Suenaga N, Narita Y, Jono H, Saito H, Kitamura K, Mukoyama M
-
Journal Title
Am J Physiol Renal Physiol
Volume: 315
Issue: 5
Pages: 1347-1357
DOI
Related Report
Peer Reviewed
-
-
-
-
-
-
-
[Presentation] Effects of aldosterone on the expression of Rhcg, an ammonia transporter, in intercalated cells of the collecting duct under metabolic acidosis.2019
Author(s)
Izumi Y, Eguchi K, Hiramatsu A, Ono M, Nakayama Y, Inoue H, Nonoguchi H, Kakizoe Y, Kuwabara T, Mukoyama M.
Organizer
第56回欧州腎臓学会議・欧州透析移植学会議
Related Report
Int'l Joint Research
-
-
-
-
-
-
-
-
-
[Presentation] Intraglomerular cross-talk between mesangial cells and podocytes inhibits normal ER-associated degradation processes and induces podocyte injury in diabetic nephropathy.2018
Author(s)
Fujimoto D, Kuwabara T, HataY, Umemoto S, Kanki T, Nishiguchi Y, Mizumoto T, Hayata M, Izumi Y, Kakizoe Y, Mukoyama M
Organizer
米国腎臓学会 Kidney Week 2018
Related Report
Int'l Joint Research
-
[Presentation] Osteocrin, a bone-derived humoral factor, exerts a renoprotective role in ischemia-reperfusion injury in mice.2018
Author(s)
Nishiguchi Y, Kuwabara T, Umemoto S, Fujimoto D, Kanki T, Hata Y, Yokoi H, Izumi Y, Kakizoe Y, Mukoyama M
Organizer
米国腎臓学会 Kidney Week 2018
Related Report
Int'l Joint Research
-
-
-
-
-
-
-
-
-