PMID- 11967018
OWN - NLM
STAT- MEDLINE
DCOM- 20021028
LR  - 20211203
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 61
IP  - 5
DP  - 2002 May
TI  - Y-27632 prevents tubulointerstitial fibrosis in mouse kidneys with unilateral 
      ureteral obstruction.
PG  - 1684-95
AB  - BACKGROUND: The small GTPase Rho is involved in cell-to-substratum adhesion and 
      cell contraction. These actions of Rho mediated by downstream Rho effectors such 
      as Rho-associated coiled-coil forming protein kinase (ROCK) may be partly 
      responsible for the progression of renal interstitial fibrosis. METHODS: The 
      anti-fibrosis effects of Y-27632, a specific ROCK inhibitor, were studied both in 
      vivo (unilateral ureteral obstruction; UUO) and in vitro. To investigate the 
      therapeutic efficacy of Y-27632 in UUO kidneys, smooth muscle alpha actin 
      (SMalphaA) expression, macrophage infiltration and fibrosis in the obstructed 
      kidneys were studied. SMalphaA, transforming growth factor beta (TGF-beta), 
      alpha1 (I) collagen, osteopontin, macrophage chemoattractant peptide-1 (MCP-1), 
      and intercellular adhesion molecule-1 (ICAM-1) gene expression were examined by 
      Northern blotting. To elucidate the mechanism linking the Rho-ROCK pathway with 
      renal fibrosis, the effects of Y-27632 on in vitro cell proliferation and cell 
      migration were studied. RESULTS: In vivo analysis showed that Y-27632 suppressed 
      SMalphaA expression, macrophage infiltration and interstitial fibrosis, and that 
      Y-27632 suppressed SMalphaA, TGF-beta and alpha1 (I) collagen mRNA expression. In 
      vitro analysis showed that Y-27632 did not suppress proliferation of renal 
      fibroblasts but suppressed migration of macrophages. CONCLUSIONS: The Rho-ROCK 
      system may play an important role in the development of tissue fibrosis, and the 
      Rho-ROCK signaling pathway may be a new therapeutic target for preventing 
      interstitial fibrosis in progressive renal disease.
FAU - Nagatoya, Katsuyuki
AU  - Nagatoya K
AD  - Department of Internal Medicine and Therapeutics, Osaka University Graduate 
      School of Medicine, and School ofHealth and Sport Sciences, Osaka University, 
      Osaka, Japan.
FAU - Moriyama, Toshiki
AU  - Moriyama T
FAU - Kawada, Noritaka
AU  - Kawada N
FAU - Takeji, Masanobu
AU  - Takeji M
FAU - Oseto, Susumu
AU  - Oseto S
FAU - Murozono, Takahiro
AU  - Murozono T
FAU - Ando, Akio
AU  - Ando A
FAU - Imai, Enyu
AU  - Imai E
FAU - Hori, Masatsugu
AU  - Hori M
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Actins)
RN  - 0 (Amides)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Pyridines)
RN  - 0 (RNA, Messenger)
RN  - 138381-45-0 (Y 27632)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (rho-Associated Kinases)
RN  - EC 3.6.5.2 (Rhoc protein, mouse)
RN  - EC 3.6.5.2 (ras Proteins)
RN  - EC 3.6.5.2 (rho GTP-Binding Proteins)
RN  - EC 3.6.5.2 (rhoA GTP-Binding Protein)
RN  - EC 3.6.5.2 (rhoB GTP-Binding Protein)
RN  - EC 3.6.5.2 (rhoC GTP-Binding Protein)
SB  - IM
MH  - Actins/genetics
MH  - Administration, Oral
MH  - Amides/*pharmacology
MH  - Animals
MH  - Cell Division/drug effects
MH  - Cell Movement/drug effects/immunology
MH  - Cells, Cultured
MH  - Enzyme Inhibitors/*pharmacology
MH  - Fibroblasts/cytology/physiology
MH  - Fibrosis
MH  - Gene Expression/drug effects
MH  - Intracellular Signaling Peptides and Proteins
MH  - Kidney/*pathology
MH  - Macrophages/cytology/drug effects
MH  - Mice
MH  - Nephritis, Interstitial/*drug therapy/pathology/prevention & control
MH  - Protein Serine-Threonine Kinases/antagonists & inhibitors/genetics
MH  - Pyridines/*pharmacology
MH  - RNA, Messenger/analysis
MH  - Signal Transduction/drug effects
MH  - Ureteral Obstruction/complications/*pathology
MH  - ras Proteins
MH  - rho GTP-Binding Proteins/genetics
MH  - rho-Associated Kinases
MH  - rhoA GTP-Binding Protein/genetics
MH  - rhoB GTP-Binding Protein/genetics
MH  - rhoC GTP-Binding Protein
EDAT- 2002/04/23 10:00
MHDA- 2002/10/29 04:00
CRDT- 2002/04/23 10:00
PHST- 2002/04/23 10:00 [pubmed]
PHST- 2002/10/29 04:00 [medline]
PHST- 2002/04/23 10:00 [entrez]
AID - S0085-2538(15)48405-4 [pii]
AID - 10.1046/j.1523-1755.2002.00328.x [doi]
PST - ppublish
SO  - Kidney Int. 2002 May;61(5):1684-95. doi: 10.1046/j.1523-1755.2002.00328.x.