TY - JOUR
T1 - Fasudil attenuates interstitial fibrosis in rat kidneys with unilateral ureteral obstruction
AU - Satoh, Shin ichi
AU - Yamaguchi, Tamami
AU - Hitomi, Asako
AU - Sato, Norihiro
AU - Shiraiwa, Kazumi
AU - Ikegaki, Ichiro
AU - Asano, Toshio
AU - Shimokawa, Hiroaki
PY - 2002/11/29
Y1 - 2002/11/29
N2 - 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.
AB - 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.
KW - Fasudil
KW - Macrophage
KW - Renal interstitial fibrosis
KW - Rho-kinase
KW - Unilateral ureteral obstruction
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U2 - 10.1016/S0014-2999(02)02619-5
DO - 10.1016/S0014-2999(02)02619-5
M3 - Article
C2 - 12445583
AN - SCOPUS:0037195584
SN - 0014-2999
VL - 455
SP - 169
EP - 174
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 2-3
ER -