| First Author | Hamasaki Y | Year | 2013 |
| Journal | Am J Physiol Renal Physiol | Volume | 305 |
| Issue | 12 | Pages | F1796-803 |
| PubMed ID | 24107419 | Mgi Jnum | J:204581 |
| Mgi Id | MGI:5532853 | Doi | 10.1152/ajprenal.00151.2013 |
| Citation | Hamasaki Y, et al. (2013) A 5-hydroxytryptamine receptor antagonist, sarpogrelate, reduces renal tubulointerstitial fibrosis by suppressing PAI-1. Am J Physiol Renal Physiol 305(12):F1796-803 |
| abstractText | A selective 5-hydroxytryptamine (5-HT) 2A receptor antagonist sarpogrelate (SG) blocks serotonin-induced platelet aggregation. It has been used clinically for the treatment of peripheral arterial disease. SG might be able to improve chronic ischemia, which contributes to renal fibrosis progression by maintaining renal microcirculation. This study investigated whether SG suppresses renal fibrosis. C57BL/6 mice fed a 0.2% adenine-containing diet for 6 wk developed severe tubulointerstitial fibrosis with kidney dysfunction. Subsequent SG treatment (30 mg.kg(-1).day(-1)) for 4 wk improved these changes significantly by increasing peritubular blood flow in the fibrotic area, as evaluated by intravital microscopy and decreasing fibrin deposition. Urinary L-type fatty acid-binding protein, up-regulated by renal hypoxia, was also reduced by SG. Additionally, results showed that mRNA expression of plasminogen activator inhibitor-1 (PAI-1), which is known to promote fibrosis by mediating and enhancing transforming growth factor (TGF)-beta1 signaling, was suppressed by SG treatment in the kidney. In vitro experiments using cultured murine proximal tubular epithelial (mProx) cells revealed that incubation with TGF-beta1 and 5-HT increased PAI-1 mRNA expression; SG significantly reduced it. In conclusion, SG reduces renal fibrosis not only by the antithrombotic effect of maintaining peritubular blood flow but also by suppressing PAI-1 expression in renal tubular cells. |
