PMID- 11422736
OWN - NLM
STAT- MEDLINE
DCOM- 20010830
LR  - 20131121
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 60
IP  - 1
DP  - 2001 Jul
TI  - High glucose induces MCP-1 expression partly via tyrosine kinase-AP-1 pathway in 
      peritoneal mesothelial cells.
PG  - 55-64
AB  - BACKGROUND: High glucose in peritoneal dialysis solutions has been implicated in 
      the pathogenesis of peritoneal fibrosis in chronic ambulatory peritoneal dialysis 
      (CAPD) patients. However, the mechanisms are not very clear. Peritoneal 
      macrophages seem to participate in the process of peritoneal fibrosis and 
      monocyte chemoattractant protein-1 (MCP-1) plays a key role in the recruitment of 
      monocytes toward the peritoneal cavity. However, little is known about the effect 
      of high glucose on MCP-1 expression and its signal transduction pathway in human 
      peritoneal mesothelial cells. METHODS: Mesothelial cells were cultured with 
      glucose (5 to 100 mmol/L) or mannitol chronically for up to seven days. MCP-1 
      expression of mRNA and protein was measured by Northern blot analysis and 
      enzyme-linked immunosorbent assay (ELISA). Chemotactic activity of 
      high-glucose-conditioned culture supernatant was measured by chemotactic assay. 
      To examine the roles of the transcription factors activator protein-1 (AP-1) and 
      nuclear factor-kappaB (NF-kappaB), electrophoretic mobility shift assay (EMSA) 
      was performed. RESULTS: Glucose induced MCP-1 mRNA expression in a time- and 
      dose-dependent manner. MCP-1 protein in cell culture supernant was also 
      increased. Equivalent concentrations of mannitol had no significant effect. 
      High-glucose-conditioned supernatant possessed an increased chemotactic activity 
      for monocytes, which was neutralized by anti-MCP-1 antibody. EMSA revealed that 
      glucose increased the AP-1 binding activity in a time- and dose-dependent manner, 
      but not NF-kappaB. Curcumin, an inhibitor of AP-1, dose-dependently suppressed 
      the induction of MCP-1 mRNA by high glucose. Tyrosine kinase inhibitors such as 
      genistein (12.5 to 50 micromol/L) and herbimycin A (0.1 to 1 micromol/L) 
      inhibited the high-glucose-induced MCP-1 mRNA expression in a dose-dependent 
      manner, and also suppressed the high-glucose-induced AP-1 binding activity. 
      CONCLUSIONS: : High glucose induced mesothelial MCP-1 expression partly via the 
      tyrosine kinase-AP-1 pathway.
FAU - Lee, S K
AU  - Lee SK
AD  - Department of Internal Medicine, and Asan Institute for Life Sciences, University 
      of Ulsan, College of Medicine, Seoul, Korea.
FAU - Kim, B S
AU  - Kim BS
FAU - Yang, W S
AU  - Yang WS
FAU - Kim, S B
AU  - Kim SB
FAU - Park, S K
AU  - Park SK
FAU - Park, J S
AU  - Park JS
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 (RNA, Messenger)
RN  - 0 (Transcription Factor AP-1)
RN  - 3OWL53L36A (Mannitol)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Chemotaxis, Leukocyte/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Epithelial Cells/drug effects/metabolism
MH  - Gene Expression/drug effects/physiology
MH  - Glucose/*administration & dosage/pharmacology
MH  - Humans
MH  - Mannitol/pharmacology
MH  - Monocytes/physiology
MH  - Peritoneum/cytology/*drug effects/*metabolism
MH  - Protein-Tyrosine Kinases/*metabolism/physiology
MH  - RNA, Messenger/metabolism
MH  - Transcription Factor AP-1/*metabolism/physiology
EDAT- 2001/06/26 10:00
MHDA- 2001/08/31 10:01
CRDT- 2001/06/26 10:00
PHST- 2001/06/26 10:00 [pubmed]
PHST- 2001/08/31 10:01 [medline]
PHST- 2001/06/26 10:00 [entrez]
AID - S0085-2538(15)47819-6 [pii]
AID - 10.1046/j.1523-1755.2001.00770.x [doi]
PST - ppublish
SO  - Kidney Int. 2001 Jul;60(1):55-64. doi: 10.1046/j.1523-1755.2001.00770.x.