Podocyte-tubular epithelial cell interaction plays a role to prevent tubular injury
| Project/Area Number |
15H04836
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | University of Fukui |
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Principal Investigator |
Iwano Masayuki 福井大学, 学術研究院医学系部門, 教授 (20275324)
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| Co-Investigator(Kenkyū-buntansha) |
松阪 泰二 東海大学, 医学部, 教授 (50317749)
栗原 秀剛 藍野大学, 医療保健学部, 教授 (80311976)
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2016: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
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| Keywords | FSP1 / ポドサイト / 尿細管上皮細胞 / Nrf2 / 抗酸化作用 / 急性腎障害 / AKI / シスプラチン腎症 / HO-1 / チオレドキシン / SOD / RAGE / エクソソーム / ＦＳＰ１ / バイオマーカー / 糸球体腎炎 / 半月体 / 尿細管障害 |
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| Outline of Final Research Achievements |
In human active glomerulonephritis, fibroblast specific protein 1 (FSP1) was highly expressed in podocytes. In this study, we investigated biological effects of FSP1 which can be excreted from podocytes in vitro and in vivo. Recombinant FSP1 (rFSP1) induced HO-1, SOD, and thioredoxin expression in tubular epithelial cells (TEC) via Nrf2 activation and rFSP1 exerted antioxidant effects and anti-apoptotic effects on TEC. rFSP1 could ameliorate acute tubular injury in cisplatin nephrotoxicity. In transgenic mice in which FSP1 was specifically expressed in podocytes, tubular injury in cisplatin nephrotoxicity was also ameliorated, which suggests podocyte-TEC interaction.
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| Academic Significance and Societal Importance of the Research Achievements |
AKIは生命予後を著明に低下させる重要な病態である。しかし現在のところAKIに対する有効な予防薬および治療薬が存在しないため、世界中で精力的に研究が行われている。分泌型FSP1は、抗炎症作用、抗アポトーシス作用および抗酸化作用を併せ持つことから、AKI新規治療薬として有望である。増加の一途を辿る透析患者数に歯止めをかけるために、腎臓病領域における新薬開発は喫緊の課題である。本研究は、創薬に直結する意義深いものである。
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Report
(5 results)
Research Products
(18 results)
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[Journal Article] Elevated Levels of Urinary Extracellular Vesicle Fibroblast-Specific Protein 1 in Patients with Active Crescentic Glomerulonephritis.2019
Author(s)
Morikawa Y, Takahashi N, Kamiyama K, Nishimori K, Nishikawa Y, Morita S, Kobayashi M, Fukushima S, Yokoi S, Mikami D, Kimura H, Kasuno K, Yashiki T, Naiki H, Hara M, Iwano M.
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Journal Title
Nephron
Volume: 141
Issue: 3
Pages: 177-187
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] The age-related changes of dietary phosphate responsiveness in plasma 1,25-dihydroxyvitamin D levels and renal Cyp27b1 and Cyp24a1 gene expression is associated with renal α-Klotho gene expression in mice2018
Author(s)
Yoshikawa R, Yamamoto H, Nakahashi O, Kagawa T, Tajiri M, Nakao M, Fukuda S, Arai H, Masuda M, Iwano M, Takeda E, Taketani Y.
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Journal Title
Journal of Clinical Biochemistry and Nutrition
Volume: 62
Issue: 1
Pages: 68-74
DOI
NAID
ISSN
0912-0009, 1880-5086
Related Report
Peer Reviewed / Open Access
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[Journal Article] Short-chain fatty acids, GPR41 and GPR43 ligands, inhibit TNF-α-induced MCP-1 expression by modulating p38 and JNK signaling pathways in human renal cortical epithelial cells.2017
Author(s)
Kobayashi M, Mikami D, Kimura H, Kamiyama K, Morikawa Y, Yokoi S, Kasuno K, Takahashi N, Taniguchi T, Iwano M.
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Journal Title
Biochem Biophys Res Commun.
Volume: 486
Issue: 2
Pages: 499-505
DOI
Related Report
Peer Reviewed
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[Journal Article] Mizoribine therapy combined with steroids and mizoribine blood concentration monitoring for idiopathic membranous nephropathy with steroid-resistant nephrotic syndrome.2017
Author(s)
Saito T, Iwano M, Matsumoto K, Mitarai T, Yokoyama H, Yorioka N, Nishi S, Yoshimura A, Sato H, Ogahara S, Sasatomi Y, Kataoka Y, Ueda S, Koyama A, Maruyama S, Nangaku M, Imai E, Matsuo S, Tomino Y; Refractory Nephrotic Syndrome Study Group.
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Journal Title
Clin Exp Nephrol.
Volume: 21
Issue: 6
Pages: 961-970
DOI
NAID
Related Report
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[Journal Article] Mizoribine therapy combined with steroids and mizoribine blood concentration monitoring for idiopathic membranous nephropathy with steroid-resistant nephrotic syndrome.2017
Author(s)
Saito T, Iwano M, Matsumoto K, Mitarai T, Yokoyama H, Yorioka N, Nishi S, Yoshimura A, Sato H, Ogahara S, Sasatomi Y, Kataoka Y, Ueda S, Koyama A, Maruyama S, Nangaku M, Imai E, Matsuo S, Tomino Y
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Journal Title
Clin Exp Nephrol
Volume: 印刷中
NAID
Related Report
Peer Reviewed
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[Presentation] Intracellular Thioredoxin Depletion Triggers Tubular Epithelial G2/M arrest in Acute Kidney Injury2018
Author(s)
Kenji Kasuno, Seiji Yokoi, Naoki Takahashi, Daisuke Mikami, Kazuhisa Nishimori, Sachiko Fukushima, Yukie Morikawa, Mamiko Kobayashi, Sayu Morita, Hideki Kimura, Masayuki Iwano
Organizer
日本腎臓学会学術総会
Related Report
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[Presentation] Elevated Levels of Urinary Extracellular Vesicle Fibroblast-Specific Protein 1 in Patients with Active Crescentic Glomerulonephritis2018
Author(s)
Morikawa Y, Takahashi N, Kamiyama K, Nishimori K, Nishikawa Y, Morita S, Kobayashi M, Fukushima S, Yokoi S, Mikami D, Kimura H, Kasuno K, Iwano M.
Organizer
Kidney Week 2018
Related Report
Int'l Joint Research
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