2016 Fiscal Year Final Research Report
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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| Keywords | 線維化 / 腎臓 |
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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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| Free Research Field |
腎臓内科
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