PMID- 22949384
OWN - NLM
STAT- MEDLINE
DCOM- 20130604
LR  - 20211203
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Linking)
VI  - 114
IP  - 2
DP  - 2013 Feb
TI  - Celastrol attenuates adipokine resistin-associated matrix interaction and 
      migration of vascular smooth muscle cells.
PG  - 398-408
LID - 10.1002/jcb.24374 [doi]
AB  - Obesity instigates various health problems such as atherosclerosis, diabetes, and 
      cancer. Resistin, an adipose tissue-specific secretory adipokine, operates 
      endocrine functions through increasing insulin resistance. Vascular smooth muscle 
      cells (SMC) migrate into the subendothelial space and proliferate, thereby 
      contributing to neointimal formation in atherosclerosis and restenosis. The aim 
      of this study was to elucidate whether celastrol obtained from Tripterygium 
      wilfordii Hook, inhibited human aortic SMC migration. Celastrol capable of 
      antagonizing inflammatory responses attenuated the resistin secretion from 
      THP-1-derived macrophages. The macrophage-conditioned media promoted SMC 
      proliferation and MMP-2 production, which was dampened by 10-100 nM celastrol. 
      Celastrol encumbered the SMC migration in response to 50 ng/ml resistin, 
      concomitant with the inhibition of induction of connective tissue growth factor 
      and collagen I/IV. In addition, celastrol disabled human aortic SMC exposed to 
      resistin from migrating. The resistin-induced shedding of integrin beta2/beta3 
      expression was demoted by celastrol, thereby contributing to the inhibition of 
      collagen matrix-SMC interaction. Next, resistin-induced Toll-like receptor-4 
      (TLR-4) expression was abrogated by celastrol, indicating that TLR-4 was the 
      resistin signaling receptor that was blocked by celastrol. Collectively, these 
      results demonstrate that anti-inflammatory celastrol blunted the macrophage 
      secretion of the adipokine resistin, and suppressed the SMC migration by 
      disturbing the interaction between SMC and intimal collagen matrix. Therefore, 
      celastrol may inhibit atherogenic migration of vascular SMC upon resistin loading 
      by intimal macrophages within atherosclerotic lesions.
CI  - Copyright (c) 2012 Wiley Periodicals, Inc.
FAU - Kang, Sang-Wook
AU  - Kang SW
AD  - Department of Food and Nutrition, Hallym University, Chuncheon, Republic of 
      Korea.
FAU - Kim, Min Soo
AU  - Kim MS
FAU - Kim, Hyun-Sung
AU  - Kim HS
FAU - Kim, Yunho
AU  - Kim Y
FAU - Shin, Daekeun
AU  - Shin D
FAU - Park, Jung Han Yoon
AU  - Park JH
FAU - Kang, Young-Hee
AU  - Kang YH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (Collagen Type IV)
RN  - 0 (Pentacyclic Triterpenes)
RN  - 0 (Resistin)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Triterpenes)
RN  - L8GG98663L (celastrol)
SB  - IM
MH  - Aorta/cytology/drug effects
MH  - Atherosclerosis/*metabolism
MH  - Cell Movement/drug effects
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Collagen Type IV/metabolism
MH  - Gene Expression/drug effects
MH  - Humans
MH  - *Insulin Resistance/genetics
MH  - Macrophages/metabolism
MH  - *Muscle, Smooth, Vascular/cytology/metabolism
MH  - Pentacyclic Triterpenes
MH  - Resistin/*metabolism
MH  - Toll-Like Receptor 4/metabolism
MH  - Tripterygium
MH  - Triterpenes/*administration & dosage
EDAT- 2012/09/06 06:00
MHDA- 2013/06/05 06:00
CRDT- 2012/09/06 06:00
PHST- 2012/05/29 00:00 [received]
PHST- 2012/08/22 00:00 [accepted]
PHST- 2012/09/06 06:00 [entrez]
PHST- 2012/09/06 06:00 [pubmed]
PHST- 2013/06/05 06:00 [medline]
AID - 10.1002/jcb.24374 [doi]
PST - ppublish
SO  - J Cell Biochem. 2013 Feb;114(2):398-408. doi: 10.1002/jcb.24374.