Fasudil attenuates interstitial fibrosis in rat kidneys with unilateral ureteral obstruction

Shin ichi Satoh, Tamami Yamaguchi, Asako Hitomi, Norihiro Sato, Kazumi Shiraiwa, Ichiro Ikegaki, Toshio Asano, Hiroaki Shimokawa

Research output: Contribution to journalArticlepeer-review

78 Citations (Scopus)

Abstract

This study was designed to investigate possible effects of the Rho-kinase inhibitor, fasudil, on the progression of renal failure in rats with unilateral ureteral obstruction. The renal failure markers monitored were the extent of renal interstitial fibrosis and that of macrophage infiltration. In kidneys with unilateral ureteral obstruction, interstitial fibrosis was observed, using Sirius-Red staining, on day 16 after unilateral ureteral obstruction. Macrophage infiltration was observed by immunohistochemistry, using the antibody, ED1. Interstitial fibrosis and macrophage infiltration were significantly attenuated in fasudil-treated animals. The migration of monocytes in vitro elicited by N-formyl-methionyl-leucyl-phenylalanine was potently inhibited by fasudil and its active metabolite, hydroxyfasudil. These results suggest that inhibition of Rho-kinase produces a reduction of macrophage infiltration and represents a new therapeutic strategy for renal fibrosis, a major factor in the progression to end-stage renal failure.

Original languageEnglish
Pages (from-to)169-174
Number of pages6
JournalEuropean Journal of Pharmacology
Volume455
Issue number2-3
DOIs
Publication statusPublished - 2002 Nov 29

Keywords

  • Fasudil
  • Macrophage
  • Renal interstitial fibrosis
  • Rho-kinase
  • Unilateral ureteral obstruction

ASJC Scopus subject areas

  • Pharmacology

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