| Project/Area Number |
25860288
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Experimental pathology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Research Collaborator |
NOIRI Eisei
DOI Kent
OGASAWARA Emi
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 腎尿細管間質線維化 / 5-HT受容体拮抗薬 / PAI-1 / 近位尿細管上皮細胞 / L-FABP / 傍尿細管血流 / 腎線維化 / 尿細管上皮細胞 |
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| Outline of Final Research Achievements |
We investigated whether a selective 5-hydroxytryptamine (5-HT) 2A receptor antagonist sarpogrelate (SG) suppresses renal fibrosis. Mice fed an adenine-containing diet developed severe tubulointerstitial fibrosis with renal dysfunction. SG treatment improved these changes significantly accompanied with increasing peritubular blood flow, decreasing fibrin deposition, and improving inflammatory cells infiltration. Plasminogen activator inhibitor-1 (PAI-1) which is known to promote fibrosis was suppressed by SG treatment in the kidney. Urinary L-type fatty acid-binding protein was reduced by SG. In vitro experiments using cultured murine proximal tubular epithelial (mProx) cells revealed that incubation with TGF-1 and 5-HT increased PAI-1 expression; SG significantly reduced it. The receptor of SG was expressed both in the kidney and mProx cells. In conclusion, SG reduces renal fibrosis not only by the antithrombotic effect but also by suppressing PAI-1 in renal tubular epithelial cells.
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