PMID- 12846738
OWN - NLM
STAT- MEDLINE
DCOM- 20040326
LR  - 20121115
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 64
IP  - 2
DP  - 2003 Aug
TI  - Integrins induce expression of monocyte chemoattractant protein-1 via focal 
      adhesion kinase in mesangial cells.
PG  - 431-40
AB  - BACKGROUND: Integrins are major adhesion receptors that not only regulate 
      cytoskeletal organization, but also trigger a variety of intracellular signal 
      transduction pathways. We examined the effects of increased extracellular matrix 
      (ECM) accumulation on monocyte chemoattractant protein-1 (MCP-1) expression, 
      which is known to play an important role in the progression of various glomerular 
      diseases. METHODS: MCP-1 mRNA and protein expression in cultured rat mesangial 
      cells (MC) attached to ECM proteins were examined by reverse transcription 
      (RT)-polymerase chain reaction (PCR) and Western blotting, respectively. 
      Phosphorylation of focal adhesion kinase (FAK) was measured by Western blotting. 
      Effects of wild-type and dominant-negative FAK on MCP-1 expression were examined 
      by a transient transfection assay. RESULTS: Cell adhesion to fibronectin-induced 
      phosphorylation of FAK and MCP-1 mRNA expression in time- and dose-dependent 
      manners followed by increased MCP-1 protein expression. All integrin-interacting 
      substrates (laminin and types I, III, and IV collagens) also increased levels of 
      FAK phosphorylation and MCP-1 expression, whereas nonspecific adhesive substrates 
      (polylysine and concanavalin A) had no significant effects. Overexpression of 
      wild-type FAK increased phosphorylation of FAK and expression of MCP-1 mRNA and 
      protein, whereas transfection of dominant-negative FAK abolished adhesion-induced 
      MCP-1 expression. Adhesion-induced expression of MCP-1 mRNA was inhibited by 
      genistein and tosyl phenylalanyl chloromethylketone (TPCK), suggesting that 
      tyrosine kinases [e.g., FAK, and nuclear factor kappa B (NF-kappa B)] are 
      necessary in this signaling. CONCLUSION: Our results indicate that 
      integrin-mediated cell adhesion to the ECM can induce MCP-1 expression through 
      activation of FAK, and suggest a role for altered ECM deposition in the 
      progression of glomerular diseases by affecting gene expression.
FAU - Watanabe, Yujiro
AU  - Watanabe Y
AD  - Second Department of Internal Medicine, University of Occupational and 
      Environmental Health, School of Medicine, Yahatanishi, Kitakyushu, Japan.
FAU - Tamura, Masahito
AU  - Tamura M
FAU - Osajima, Akihiko
AU  - Osajima A
FAU - Anai, Hirofumi
AU  - Anai H
FAU - Kabashima, Narutoshi
AU  - Kabashima N
FAU - Serino, Ryota
AU  - Serino R
FAU - Nakashima, Yasuhide
AU  - Nakashima Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Chemokine CCL2)
RN  - 0 (Integrins)
RN  - 0 (Protein Synthesis Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - 402-71-1 (Tosylphenylalanyl Chloromethyl Ketone)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Focal Adhesion Kinase 1)
RN  - EC 2.7.10.2 (Focal Adhesion Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (Ptk2 protein, rat)
SB  - IM
MH  - Animals
MH  - Cell Adhesion/physiology
MH  - Cells, Cultured
MH  - Chemokine CCL2/antagonists & inhibitors/*genetics
MH  - Extracellular Matrix/metabolism
MH  - Focal Adhesion Kinase 1
MH  - Focal Adhesion Protein-Tyrosine Kinases
MH  - Gene Expression/physiology
MH  - Glomerular Mesangium/cytology/*physiology
MH  - Integrins/*metabolism
MH  - Male
MH  - Protein Synthesis Inhibitors/pharmacology
MH  - Protein-Tyrosine Kinases/*metabolism
MH  - RNA, Messenger/analysis
MH  - Rats
MH  - Rats, Wistar
MH  - Tosylphenylalanyl Chloromethyl Ketone/pharmacology
EDAT- 2003/07/09 05:00
MHDA- 2004/03/27 05:00
CRDT- 2003/07/09 05:00
PHST- 2003/07/09 05:00 [pubmed]
PHST- 2004/03/27 05:00 [medline]
PHST- 2003/07/09 05:00 [entrez]
AID - S0085-2538(15)49349-4 [pii]
AID - 10.1046/j.1523-1755.2003.00122.x [doi]
PST - ppublish
SO  - Kidney Int. 2003 Aug;64(2):431-40. doi: 10.1046/j.1523-1755.2003.00122.x.