PMID- 20977889
OWN - NLM
STAT- MEDLINE
DCOM- 20110113
LR  - 20101129
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 402
IP  - 4
DP  - 2010 Nov 26
TI  - Rho-kinase mediates TNF-alpha-induced MCP-1 expression via p38 MAPK signaling pathway 
      in mesangial cells.
PG  - 725-30
LID - 10.1016/j.bbrc.2010.10.093 [doi]
AB  - Macrophage accumulation has been implicated in the pathogenesis of inflammatory 
      glomerular disease. Monocyte chemoattractant protein-1 (MCP-1) plays a central 
      role in recruiting monocytes to the glomeruli. Tumor necrosis factor-alpha (TNF-alpha) 
      has been shown to induce MCP-1 expression in mesangial cells, although the 
      precise mechanisms remain unclear. We previously demonstrated that RhoA and its 
      effector, Rho-kinase (Rho-associated coiled-coil containing protein kinase, 
      ROCK), are involved in the pathogenesis of diabetic nephropathy. However, its 
      role in MCP-1 induction by TNF-alpha has not been elucidated. In the present study, 
      we investigated whether the Rho/Rho-kinase signaling pathway regulates the 
      TNF-alpha-mediated induction of MCP-1 in mesangial cells. Exposure of mouse mesangial 
      cells (MES-13) to TNF-alpha resulted in an increase of MCP-1 expression (by RT-PCR) 
      and secretion into the medium (by ELISA). Pull down and Western blot analysis 
      revealed that TNF-alpha activated RhoA and Rho-kinase. Based on these observations, 
      we speculated that the Rho/Rho-kinase signaling pathway may be involved in MCP-1 
      induction by TNF-alpha. In agreement with this concept, Y-27632, a specific 
      Rho-kinase inhibitor, attenuated TNF-alpha-mediated induction of MCP-1. We 
      demonstrated that Y-27632 inhibited TNF-alpha-mediated monocyte migration and 
      attenuated TNF-alpha-mediated p38 MAPK activation. Based on these data we infer that 
      Y-27632 inhibits TNF-alpha-induced MCP-1 expression, secretion and function through 
      inhibition of Rho-kinase and p38 MAPK activity. Our study suggests that 
      Rho/Rho-kinase is an important therapeutic target of monocyte recruitment and 
      accumulation within the glomerulus in inflammatory renal disease.
CI  - Copyright (c) 2010 Elsevier Inc. All rights reserved.
FAU - Matoba, Keiichiro
AU  - Matoba K
AD  - Division of Diabetes, Metabolism and Endocrinology, Department of Internal 
      Medicine, Jikei University School of Medicine, Tokyo, Japan.
FAU - Kawanami, Daiji
AU  - Kawanami D
FAU - Ishizawa, Sho
AU  - Ishizawa S
FAU - Kanazawa, Yasushi
AU  - Kanazawa Y
FAU - Yokota, Tamotsu
AU  - Yokota T
FAU - Utsunomiya, Kazunori
AU  - Utsunomiya K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101025
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Amides)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Pyridines)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 138381-45-0 (Y 27632)
RN  - EC 2.7.11.1 (rho-Associated Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Amides/pharmacology
MH  - Animals
MH  - Cell Line
MH  - Chemokine CCL2/*metabolism
MH  - Chemotaxis
MH  - Enzyme Inhibitors/pharmacology
MH  - Glomerulonephritis/metabolism
MH  - Mesangial Cells/drug effects/*metabolism
MH  - Mice
MH  - Pyridines/pharmacology
MH  - Signal Transduction
MH  - Tumor Necrosis Factor-alpha/pharmacology/physiology
MH  - p38 Mitogen-Activated Protein Kinases/*metabolism
MH  - rho-Associated Kinases/antagonists & inhibitors/*metabolism
EDAT- 2010/10/28 06:00
MHDA- 2011/01/14 06:00
CRDT- 2010/10/28 06:00
PHST- 2010/10/17 00:00 [received]
PHST- 2010/10/19 00:00 [accepted]
PHST- 2010/10/28 06:00 [entrez]
PHST- 2010/10/28 06:00 [pubmed]
PHST- 2011/01/14 06:00 [medline]
AID - S0006-291X(10)01982-0 [pii]
AID - 10.1016/j.bbrc.2010.10.093 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2010 Nov 26;402(4):725-30. doi: 
      10.1016/j.bbrc.2010.10.093. Epub 2010 Oct 25.