PMID- 20438710
OWN - NLM
STAT- MEDLINE
DCOM- 20100707
LR  - 20171116
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 396
IP  - 2
DP  - 2010 May 28
TI  - Nifedipine, a calcium channel blocker, inhibits inflammatory and fibrogenic gene 
      expressions in advanced glycation end product (AGE)-exposed fibroblasts via 
      mineralocorticoid receptor antagonistic activity.
PG  - 566-70
LID - 10.1016/j.bbrc.2010.04.149 [doi]
AB  - Advanced glycation end products (AGE) are involved in tissue damage and 
      remodeling. This study investigated whether AGE could elicit inflammatory and 
      fibrogenic reactions in fibroblast cell line MRC-5 cells via autocrine production 
      of aldosterone and if nifedipine could block the AGE actions through 
      mineralocorticoid receptor (MR) antagonistic activity. AGE significantly 
      up-regulated monocyte chemoattractant protein-1 (MCP-1), transforming growth 
      factor-beta (TGF-beta), type III collagen and receptor for AGE (RAGE) mRNA levels 
      in MRC-5 cells, all of which were completely blocked by nifedipine or an MR 
      antagonist spironolactone. Aldosterone also dose-dependently increased MCP-1, 
      TGF-beta and type III collagen mRNA levels in MRC-5 cells, which were suppressed 
      by nifedipine, but not amlodipine, a control calcium channel blocker. Further, 
      AGE significantly stimulated aldosterone generation in MRC-5 cells, which was 
      partially blocked by nifedipine or spironolactone. In this study, we demonstrated 
      for the first time that AGE could evoke inflammatory and fibrogenic reactions in 
      MRC-5 cells via aldosterone production, which were blocked by the MR antagonistic 
      activity of nifedipine. Our present study provides a unique beneficial aspect of 
      nifedipine on tissue damage and remodeling; it could work as an anti-inflammatory 
      and anti-fibrogenic agent against AGE via MR antagonistic activity.
CI  - Copyright (c) 2010 Elsevier Inc. All rights reserved.
FAU - Matsui, Takanori
AU  - Matsui T
AD  - Department of Pathophysiology and Therapeutics of Diabetic Vascular 
      Complications, Kurume University School of Medicine, Kurume, Japan.
FAU - Takeuchi, Masayoshi
AU  - Takeuchi M
FAU - Yamagishi, Sho-ichi
AU  - Yamagishi S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100508
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Glycation End Products, Advanced)
RN  - 0 (Mineralocorticoid Receptor Antagonists)
RN  - 4964P6T9RB (Aldosterone)
RN  - I9ZF7L6G2L (Nifedipine)
SB  - IM
MH  - Aldosterone/metabolism
MH  - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology
MH  - Calcium Channel Blockers/*pharmacology
MH  - Cell Line
MH  - Fibroblasts/*drug effects/metabolism/pathology
MH  - Fibrosis
MH  - Gene Expression/drug effects
MH  - Glycation End Products, Advanced/*metabolism/toxicity
MH  - Humans
MH  - Inflammation/chemically induced/*metabolism
MH  - *Mineralocorticoid Receptor Antagonists
MH  - Nifedipine/*pharmacology
EDAT- 2010/05/05 06:00
MHDA- 2010/07/08 06:00
CRDT- 2010/05/05 06:00
PHST- 2010/04/15 00:00 [received]
PHST- 2010/04/27 00:00 [accepted]
PHST- 2010/05/05 06:00 [entrez]
PHST- 2010/05/05 06:00 [pubmed]
PHST- 2010/07/08 06:00 [medline]
AID - S0006-291X(10)00844-2 [pii]
AID - 10.1016/j.bbrc.2010.04.149 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2010 May 28;396(2):566-70. doi: 
      10.1016/j.bbrc.2010.04.149. Epub 2010 May 8.