Involvement of LPA1-MRTF-SRF in renal fibrosis
| Project/Area Number |
26461218
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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 |
Kidney internal medicine
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
WADA TAKASHI 金沢大学, 医学系, 教授 (40334784)
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| Research Collaborator |
Tager Andrew M.
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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 |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 線維化 / 腎臓 / LPA１ / LPA / LPA1 |
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| Outline of Final Research Achievements |
Ｆibrosis is charactereized by the expansion of the fibroblast pool, but the mechanisms driving it remain to be fully clarified. We found that lysophosphatidic acid (LPA) and its receptor (LPA1) signaling drives fibroblast proliferation and activation during the development of renal fibrosis by inducing connective tissue growth factor (CTGF). Unilateral ureteral obstruction (UUO)-induced increases in renal collagen were significantly attenuated in LPA1-deficient mice (LPA1-/-) as compared to LPA1-sufficient mice (LPA+/+), as was the accumulations of fibroblasts. CTGF was detected mainly in tubular epithelial cells, and its levels were suppressed in LPA1-/-. LPA-LPA1 signaling directly induced CTGF expression by primary proximal tubular epithelial cells (PTECs). PTEC-derived CTGF mediated renal fibroblast proliferation and myofibroblast differentiation. These results suggest that targeting LPA-LPA1 signaling could be a therapeutic strategy for renal fibrosis.
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Report
(4 results)
Research Products
(16 results)
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[Journal Article] Risk factors associated with relapse or infectious complications in Japanese patients with microscopic polyangiitis.2015
Author(s)
Kitagawa K, Furuichi K, Sagara A, Shinozaki Y, Kitajima S, Toyama T, Hara A, Iwata Y, Sakai N, Shimizu M, Kaneko S, Wada T
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Journal Title
Clin Exp Nephrol
Volume: in press
Related Report
Peer Reviewed
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[Journal Article] Association of PAX2 and Other Gene Mutations with the Clinical Manifestations of Renal Coloboma Syndrome.2015
Author(s)
Okumura T, Furuichi K, Higashide T, Sakurai M, Hashimoto S, Shinozaki Y, Hara A, Iwata Y, Sakai N, Sugiyama K, Kaneko S, Wada T.
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Journal Title
PLoS One
Volume: 10
Issue: 11
Pages: e0142843-e0142843
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Relationship between Serum Uric Acid Levels and Chronic Kidney Disease in a Japanese Cohort with Normal or Mildly Reduced Kidney Function.2015
Author(s)
Toyama T, Furuichi K, Shimizu M, Hara A, Iwata Y, Sakai N, Perkovic V, Kobayashi M, Mano T, Kaneko S, Wada T.
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Journal Title
PLoS One.
Volume: 10
Issue: 9
Pages: e0137449-e0137449
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] LPA-LPA1 signaling regulates fibroblast proliferation and myofibroblast differentiation dependent on epithelial cell-fibroblast interaction.2015
Author(s)
Norihiko Sakai, Taito Miyake, Yasutaka Kamikawa, Akihiro Sagara, Yasuyuki Shinozaki, Shinji Kitajima, Akinori Hara, Yasunori Iwata, Miho Shimizu, Kengo Furuichi, Takashi Wada
Organizer
米国腎臓学会
Place of Presentation
サンディエゴ（米国）
Year and Date
2015-11-07
Related Report
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