Mechanical stretch induces the apoptosis regulator PUMA in vascular smooth muscle cells

Wen Pin Cheng, Bao Wei Wang, Shih-Chung Chen, Hang Chang, Kou-Gi Shyu

研究成果: 雜誌貢獻文章

26 引文 (Scopus)

摘要

Aims The expression of PUMA (p53-up-regulated modulator of apoptosis), an apoptosis-regulating gene, increases during endoplasmic reticulum stress. The mechanisms by which cyclic stretch influences the regulation of PUMA in vascular smooth muscle cells (VSMCs) during apoptosis remain unclear. We hypothesized that cyclic stretch enhances PUMA expression in VSMCs undergoing apoptosis. Methods and Results Human VSMCs grown on a Flexcell I flexible membrane base were stretched via vacuum to 20 of elongation at a frequency of 1 Hz. An in vivo model of volume overload with aorta-caval shunt and pressure overload with aortic banding in adult rats was used to study PUMA expression. Cyclic stretch markedly enhanced PUMA protein and gene expression after stretch. Addition of c-jun N-terminal kinase (JNK) inhibitor SP600125 and interferon-γ (IFN-γ) antibody 30 min before stretch inhibited PUMA expression. Gel shift assay demonstrated that stretch increased the DNA binding activity of interferon regulatory factor-1 (IRF-1). SP600125, JNK small interfering RNA, and IFN-γ antibody attenuated the DNA binding activity induced by stretch. PUMA-Mut plasmid, SP600125, and IRF-1 antibody attenuated the promoter activity. Stretch increased secretion of IFN-γ from VSMCs, and conditioned media from stretched VSMCs increased PUMA protein expression. The in vivo model of aorta-caval shunt and aortic banding also showed increased PUMA protein expression in the aorta. Conclusion Cyclic mechanical stretch increases PUMA expression in cultured human VSMCs. The PUMA expression induced by stretch is mediated by IFN-γ, JNK, and IRF-1 pathways. These findings suggest that PUMA is an important mediator in VSMC apoptosis induced by stretch.
原文英語
頁(從 - 到)181-189
頁數9
期刊Cardiovascular Research
93
發行號1
DOIs
出版狀態已發佈 - 一月 1 2012

指紋

Vascular Smooth Muscle
Smooth Muscle Myocytes
Apoptosis
Interferon Regulatory Factor-1
Interferons
JNK Mitogen-Activated Protein Kinases
Aorta
Venae Cavae
Antibodies
Proteins
Endoplasmic Reticulum Stress
DNA
Conditioned Culture Medium
Vacuum
Small Interfering RNA
Plasmids

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Physiology

引用此文

Mechanical stretch induces the apoptosis regulator PUMA in vascular smooth muscle cells. / Cheng, Wen Pin; Wang, Bao Wei; Chen, Shih-Chung; Chang, Hang; Shyu, Kou-Gi.

於: Cardiovascular Research, 卷 93, 編號 1, 01.01.2012, p. 181-189.

研究成果: 雜誌貢獻文章

Cheng, WP, Wang, BW, Chen, S-C, Chang, H & Shyu, K-G 2012, 'Mechanical stretch induces the apoptosis regulator PUMA in vascular smooth muscle cells', Cardiovascular Research, 卷 93, 編號 1, 頁 181-189. https://doi.org/10.1093/cvr/cvr280
Cheng, Wen Pin ; Wang, Bao Wei ; Chen, Shih-Chung ; Chang, Hang ; Shyu, Kou-Gi. / Mechanical stretch induces the apoptosis regulator PUMA in vascular smooth muscle cells. 於: Cardiovascular Research. 2012 ; 卷 93, 編號 1. 頁 181-189.
@article{8b09d92176f541bea7a665b10afdc44e,
title = "Mechanical stretch induces the apoptosis regulator PUMA in vascular smooth muscle cells",
abstract = "Aims The expression of PUMA (p53-up-regulated modulator of apoptosis), an apoptosis-regulating gene, increases during endoplasmic reticulum stress. The mechanisms by which cyclic stretch influences the regulation of PUMA in vascular smooth muscle cells (VSMCs) during apoptosis remain unclear. We hypothesized that cyclic stretch enhances PUMA expression in VSMCs undergoing apoptosis. Methods and Results Human VSMCs grown on a Flexcell I flexible membrane base were stretched via vacuum to 20 of elongation at a frequency of 1 Hz. An in vivo model of volume overload with aorta-caval shunt and pressure overload with aortic banding in adult rats was used to study PUMA expression. Cyclic stretch markedly enhanced PUMA protein and gene expression after stretch. Addition of c-jun N-terminal kinase (JNK) inhibitor SP600125 and interferon-γ (IFN-γ) antibody 30 min before stretch inhibited PUMA expression. Gel shift assay demonstrated that stretch increased the DNA binding activity of interferon regulatory factor-1 (IRF-1). SP600125, JNK small interfering RNA, and IFN-γ antibody attenuated the DNA binding activity induced by stretch. PUMA-Mut plasmid, SP600125, and IRF-1 antibody attenuated the promoter activity. Stretch increased secretion of IFN-γ from VSMCs, and conditioned media from stretched VSMCs increased PUMA protein expression. The in vivo model of aorta-caval shunt and aortic banding also showed increased PUMA protein expression in the aorta. Conclusion Cyclic mechanical stretch increases PUMA expression in cultured human VSMCs. The PUMA expression induced by stretch is mediated by IFN-γ, JNK, and IRF-1 pathways. These findings suggest that PUMA is an important mediator in VSMC apoptosis induced by stretch.",
keywords = "Apoptosis, Cyclic stretch, p53-Up-regulated modulator of apoptosis, Smooth muscle cell",
author = "Cheng, {Wen Pin} and Wang, {Bao Wei} and Shih-Chung Chen and Hang Chang and Kou-Gi Shyu",
year = "2012",
month = "1",
day = "1",
doi = "10.1093/cvr/cvr280",
language = "English",
volume = "93",
pages = "181--189",
journal = "Cardiovascular Research",
issn = "0008-6363",
publisher = "Oxford University Press",
number = "1",

}

TY - JOUR

T1 - Mechanical stretch induces the apoptosis regulator PUMA in vascular smooth muscle cells

AU - Cheng, Wen Pin

AU - Wang, Bao Wei

AU - Chen, Shih-Chung

AU - Chang, Hang

AU - Shyu, Kou-Gi

PY - 2012/1/1

Y1 - 2012/1/1

N2 - Aims The expression of PUMA (p53-up-regulated modulator of apoptosis), an apoptosis-regulating gene, increases during endoplasmic reticulum stress. The mechanisms by which cyclic stretch influences the regulation of PUMA in vascular smooth muscle cells (VSMCs) during apoptosis remain unclear. We hypothesized that cyclic stretch enhances PUMA expression in VSMCs undergoing apoptosis. Methods and Results Human VSMCs grown on a Flexcell I flexible membrane base were stretched via vacuum to 20 of elongation at a frequency of 1 Hz. An in vivo model of volume overload with aorta-caval shunt and pressure overload with aortic banding in adult rats was used to study PUMA expression. Cyclic stretch markedly enhanced PUMA protein and gene expression after stretch. Addition of c-jun N-terminal kinase (JNK) inhibitor SP600125 and interferon-γ (IFN-γ) antibody 30 min before stretch inhibited PUMA expression. Gel shift assay demonstrated that stretch increased the DNA binding activity of interferon regulatory factor-1 (IRF-1). SP600125, JNK small interfering RNA, and IFN-γ antibody attenuated the DNA binding activity induced by stretch. PUMA-Mut plasmid, SP600125, and IRF-1 antibody attenuated the promoter activity. Stretch increased secretion of IFN-γ from VSMCs, and conditioned media from stretched VSMCs increased PUMA protein expression. The in vivo model of aorta-caval shunt and aortic banding also showed increased PUMA protein expression in the aorta. Conclusion Cyclic mechanical stretch increases PUMA expression in cultured human VSMCs. The PUMA expression induced by stretch is mediated by IFN-γ, JNK, and IRF-1 pathways. These findings suggest that PUMA is an important mediator in VSMC apoptosis induced by stretch.

AB - Aims The expression of PUMA (p53-up-regulated modulator of apoptosis), an apoptosis-regulating gene, increases during endoplasmic reticulum stress. The mechanisms by which cyclic stretch influences the regulation of PUMA in vascular smooth muscle cells (VSMCs) during apoptosis remain unclear. We hypothesized that cyclic stretch enhances PUMA expression in VSMCs undergoing apoptosis. Methods and Results Human VSMCs grown on a Flexcell I flexible membrane base were stretched via vacuum to 20 of elongation at a frequency of 1 Hz. An in vivo model of volume overload with aorta-caval shunt and pressure overload with aortic banding in adult rats was used to study PUMA expression. Cyclic stretch markedly enhanced PUMA protein and gene expression after stretch. Addition of c-jun N-terminal kinase (JNK) inhibitor SP600125 and interferon-γ (IFN-γ) antibody 30 min before stretch inhibited PUMA expression. Gel shift assay demonstrated that stretch increased the DNA binding activity of interferon regulatory factor-1 (IRF-1). SP600125, JNK small interfering RNA, and IFN-γ antibody attenuated the DNA binding activity induced by stretch. PUMA-Mut plasmid, SP600125, and IRF-1 antibody attenuated the promoter activity. Stretch increased secretion of IFN-γ from VSMCs, and conditioned media from stretched VSMCs increased PUMA protein expression. The in vivo model of aorta-caval shunt and aortic banding also showed increased PUMA protein expression in the aorta. Conclusion Cyclic mechanical stretch increases PUMA expression in cultured human VSMCs. The PUMA expression induced by stretch is mediated by IFN-γ, JNK, and IRF-1 pathways. These findings suggest that PUMA is an important mediator in VSMC apoptosis induced by stretch.

KW - Apoptosis

KW - Cyclic stretch

KW - p53-Up-regulated modulator of apoptosis

KW - Smooth muscle cell

UR - http://www.scopus.com/inward/record.url?scp=84555186795&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84555186795&partnerID=8YFLogxK

U2 - 10.1093/cvr/cvr280

DO - 10.1093/cvr/cvr280

M3 - Article

C2 - 22021910

AN - SCOPUS:84555186795

VL - 93

SP - 181

EP - 189

JO - Cardiovascular Research

JF - Cardiovascular Research

SN - 0008-6363

IS - 1

ER -