2014 Fiscal Year Final Research Report
Identification of the mechanisms and treatment of tubulointerstitial fibrosis via 5-HT - 5-HT receptor pathway
| 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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| 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 |
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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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| Free Research Field |
腎臓病学
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