Regulation of resistin by cyclic mechanical stretch in cultured rat vascular smooth muscle cells

Bao Wei Wang, Hang Chang, Kou-Gi Shyu

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Resistin has a potential role in atherosclerosis; however, the molecular mechanism underlying the increase in resistin expression in atherosclerosis remains unclear. As mechanical stretch plays an important role in atherosclerosis, in the present study we sought to investigate the cellular and molecular mechanisms underlying the regulation of resistin by cyclic mechanical stretch in VSMCs (vascular smooth muscle cells). VSMCs from thoracic aorta of adult Wistar rats were cultured and subjected to cyclic stretch. Cyclic mechanical stretch significantly increased resistin protein and mRNA expression as compared with control cells without stretch. The specific p38 MAPK (mitogen-activated protein kinase) inhibitor SB203580, the antioxidant N-acetylcysteine and p38 MAPK siRNA (small interfering RNA) attenuated the induction of resistin protein by cyclic stretch. Cyclic stretch significantly increased the phosphorylation of p38 MAPK, whereas pre-treatment with SB203580 and N-acetylcysteine significantly inhibited this effect. Cyclic stretch significantly increased ROS (reactive oxygen species) production, and pre-treatment with N-acetylcysteine significantly inhibited stretch-induced ROS production. Cyclic stretch also increased STAT3 (signal transducer and activator of transcription 3)-binding activity and resistin promoter activity, and resistin promoter activity was abolished when STAT3 in the promoter area was mutated. Pre-treatment with SB203580 and N-acetylcysteine significantly attenuated resistin promoter activity induced by cyclic stretch. Cyclic stretch increased the secretion of AngII (angiotensin II) and resistin from cultured VSMCs. Exogenous AngII increased resistin expression, and AngII receptor inhibition attenuated this effect. In conclusion, cyclic mechanical stretch increases resistin expression in cultured rat VSMCs. Stretch-induced resistin expression is mediated through ROS, and the p38 MAPK and STAT3 pathways. Therefore resistin induced by cyclic stretch may contribute to the pathogenesis of atherosclerosis under haemodynamic overload.

Original languageEnglish
Pages (from-to)221-230
Number of pages10
JournalClinical Science
Volume118
Issue number3
DOIs
Publication statusPublished - 2010

Fingerprint

Resistin
Vascular Smooth Muscle
Smooth Muscle Myocytes
Acetylcysteine
p38 Mitogen-Activated Protein Kinases
STAT3 Transcription Factor
Atherosclerosis
Reactive Oxygen Species
Angiotensin II
Angiotensin Receptors
Protein Kinase Inhibitors
Thoracic Aorta
Small Interfering RNA

Keywords

  • Atherosclerosis
  • Mitogen-activated protein kinase (MAPK)
  • Reactive oxygen species (ROS)
  • Resistin
  • Signal transducer and activator of transcription (STAT)
  • Smooth muscle cell
  • Stretch

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Regulation of resistin by cyclic mechanical stretch in cultured rat vascular smooth muscle cells. / Wang, Bao Wei; Chang, Hang; Shyu, Kou-Gi.

In: Clinical Science, Vol. 118, No. 3, 2010, p. 221-230.

Research output: Contribution to journalArticle

Wang, Bao Wei ; Chang, Hang ; Shyu, Kou-Gi. / Regulation of resistin by cyclic mechanical stretch in cultured rat vascular smooth muscle cells. In: Clinical Science. 2010 ; Vol. 118, No. 3. pp. 221-230.
@article{0d2026281053430d8f7e65ed9bc7d992,
title = "Regulation of resistin by cyclic mechanical stretch in cultured rat vascular smooth muscle cells",
abstract = "Resistin has a potential role in atherosclerosis; however, the molecular mechanism underlying the increase in resistin expression in atherosclerosis remains unclear. As mechanical stretch plays an important role in atherosclerosis, in the present study we sought to investigate the cellular and molecular mechanisms underlying the regulation of resistin by cyclic mechanical stretch in VSMCs (vascular smooth muscle cells). VSMCs from thoracic aorta of adult Wistar rats were cultured and subjected to cyclic stretch. Cyclic mechanical stretch significantly increased resistin protein and mRNA expression as compared with control cells without stretch. The specific p38 MAPK (mitogen-activated protein kinase) inhibitor SB203580, the antioxidant N-acetylcysteine and p38 MAPK siRNA (small interfering RNA) attenuated the induction of resistin protein by cyclic stretch. Cyclic stretch significantly increased the phosphorylation of p38 MAPK, whereas pre-treatment with SB203580 and N-acetylcysteine significantly inhibited this effect. Cyclic stretch significantly increased ROS (reactive oxygen species) production, and pre-treatment with N-acetylcysteine significantly inhibited stretch-induced ROS production. Cyclic stretch also increased STAT3 (signal transducer and activator of transcription 3)-binding activity and resistin promoter activity, and resistin promoter activity was abolished when STAT3 in the promoter area was mutated. Pre-treatment with SB203580 and N-acetylcysteine significantly attenuated resistin promoter activity induced by cyclic stretch. Cyclic stretch increased the secretion of AngII (angiotensin II) and resistin from cultured VSMCs. Exogenous AngII increased resistin expression, and AngII receptor inhibition attenuated this effect. In conclusion, cyclic mechanical stretch increases resistin expression in cultured rat VSMCs. Stretch-induced resistin expression is mediated through ROS, and the p38 MAPK and STAT3 pathways. Therefore resistin induced by cyclic stretch may contribute to the pathogenesis of atherosclerosis under haemodynamic overload.",
keywords = "Atherosclerosis, Mitogen-activated protein kinase (MAPK), Reactive oxygen species (ROS), Resistin, Signal transducer and activator of transcription (STAT), Smooth muscle cell, Stretch",
author = "Wang, {Bao Wei} and Hang Chang and Kou-Gi Shyu",
year = "2010",
doi = "10.1042/CS20090155",
language = "English",
volume = "118",
pages = "221--230",
journal = "Clinical Science",
issn = "0143-5221",
publisher = "Portland Press Ltd.",
number = "3",

}

TY - JOUR

T1 - Regulation of resistin by cyclic mechanical stretch in cultured rat vascular smooth muscle cells

AU - Wang, Bao Wei

AU - Chang, Hang

AU - Shyu, Kou-Gi

PY - 2010

Y1 - 2010

N2 - Resistin has a potential role in atherosclerosis; however, the molecular mechanism underlying the increase in resistin expression in atherosclerosis remains unclear. As mechanical stretch plays an important role in atherosclerosis, in the present study we sought to investigate the cellular and molecular mechanisms underlying the regulation of resistin by cyclic mechanical stretch in VSMCs (vascular smooth muscle cells). VSMCs from thoracic aorta of adult Wistar rats were cultured and subjected to cyclic stretch. Cyclic mechanical stretch significantly increased resistin protein and mRNA expression as compared with control cells without stretch. The specific p38 MAPK (mitogen-activated protein kinase) inhibitor SB203580, the antioxidant N-acetylcysteine and p38 MAPK siRNA (small interfering RNA) attenuated the induction of resistin protein by cyclic stretch. Cyclic stretch significantly increased the phosphorylation of p38 MAPK, whereas pre-treatment with SB203580 and N-acetylcysteine significantly inhibited this effect. Cyclic stretch significantly increased ROS (reactive oxygen species) production, and pre-treatment with N-acetylcysteine significantly inhibited stretch-induced ROS production. Cyclic stretch also increased STAT3 (signal transducer and activator of transcription 3)-binding activity and resistin promoter activity, and resistin promoter activity was abolished when STAT3 in the promoter area was mutated. Pre-treatment with SB203580 and N-acetylcysteine significantly attenuated resistin promoter activity induced by cyclic stretch. Cyclic stretch increased the secretion of AngII (angiotensin II) and resistin from cultured VSMCs. Exogenous AngII increased resistin expression, and AngII receptor inhibition attenuated this effect. In conclusion, cyclic mechanical stretch increases resistin expression in cultured rat VSMCs. Stretch-induced resistin expression is mediated through ROS, and the p38 MAPK and STAT3 pathways. Therefore resistin induced by cyclic stretch may contribute to the pathogenesis of atherosclerosis under haemodynamic overload.

AB - Resistin has a potential role in atherosclerosis; however, the molecular mechanism underlying the increase in resistin expression in atherosclerosis remains unclear. As mechanical stretch plays an important role in atherosclerosis, in the present study we sought to investigate the cellular and molecular mechanisms underlying the regulation of resistin by cyclic mechanical stretch in VSMCs (vascular smooth muscle cells). VSMCs from thoracic aorta of adult Wistar rats were cultured and subjected to cyclic stretch. Cyclic mechanical stretch significantly increased resistin protein and mRNA expression as compared with control cells without stretch. The specific p38 MAPK (mitogen-activated protein kinase) inhibitor SB203580, the antioxidant N-acetylcysteine and p38 MAPK siRNA (small interfering RNA) attenuated the induction of resistin protein by cyclic stretch. Cyclic stretch significantly increased the phosphorylation of p38 MAPK, whereas pre-treatment with SB203580 and N-acetylcysteine significantly inhibited this effect. Cyclic stretch significantly increased ROS (reactive oxygen species) production, and pre-treatment with N-acetylcysteine significantly inhibited stretch-induced ROS production. Cyclic stretch also increased STAT3 (signal transducer and activator of transcription 3)-binding activity and resistin promoter activity, and resistin promoter activity was abolished when STAT3 in the promoter area was mutated. Pre-treatment with SB203580 and N-acetylcysteine significantly attenuated resistin promoter activity induced by cyclic stretch. Cyclic stretch increased the secretion of AngII (angiotensin II) and resistin from cultured VSMCs. Exogenous AngII increased resistin expression, and AngII receptor inhibition attenuated this effect. In conclusion, cyclic mechanical stretch increases resistin expression in cultured rat VSMCs. Stretch-induced resistin expression is mediated through ROS, and the p38 MAPK and STAT3 pathways. Therefore resistin induced by cyclic stretch may contribute to the pathogenesis of atherosclerosis under haemodynamic overload.

KW - Atherosclerosis

KW - Mitogen-activated protein kinase (MAPK)

KW - Reactive oxygen species (ROS)

KW - Resistin

KW - Signal transducer and activator of transcription (STAT)

KW - Smooth muscle cell

KW - Stretch

UR - http://www.scopus.com/inward/record.url?scp=70549108877&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70549108877&partnerID=8YFLogxK

U2 - 10.1042/CS20090155

DO - 10.1042/CS20090155

M3 - Article

C2 - 20310085

AN - SCOPUS:70549108877

VL - 118

SP - 221

EP - 230

JO - Clinical Science

JF - Clinical Science

SN - 0143-5221

IS - 3

ER -