MicroRNA-25 protects smooth muscle cells against corticosterone-induced apoptosis

Bin Zhang, Gaoxing Zhang, Tianlu Wei, Zhen Yang, Wenfeng Tan, Ziqing Mo, Jinxue Liu, Dong Li, Yidong Wei, Lukun Zhang, Keith A. Webster, Jianqin Wei

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background and Aims. Vascular smooth muscle cells (VSMCs) are central components of atherosclerotic plaque. Loss of VSMCs through apoptotic cell death can cause fibrous cap thinning, necrotic core formation, and calcification that may destabilize plaque. Elevated glucocorticoid levels caused by psychological stress promote VSMC apoptosis and can exacerbate atherosclerosis in mice and humans. Changes in the levels of antiapoptosis microRNA-25 (miR-25) have been linked with heart disease, inflammation, VSMC phenotype, oxidative stress, and apoptosis. Here, we investigated the pathways and mechanisms of glucocorticoid-induced apoptosis of mouse VSMCs and the protective role of miR-25. Methods. Primary mouse VSMCs were cultured +/- corticosterone for 48 h. Apoptosis, ROS, apoptotic protein activities, miR-25, MOAP1, a miR-25 target, and p70S6 kinase were quantified at intervals. The roles of miR-25 were assessed by treating cells with lenti-pre-miR-25 and anti-miR-25. Results. VSMC apoptosis, caspase-3 activity, and Bax were increased by corticosterone, and cell death was paralleled by marked loss of miR-25. Protection was conferred by pre-miR-25 and exacerbated by anti-miR-25. Pre-miR-25 conferred reduced expression of the proapoptotic protein MOAP1, and the protective effects of pre-miR-25 were abrogated by overexpressing MOAP1. The antiapoptotic effects of miR-25 were paralleled by inhibition of the p70S6K pathway, a convergence target for the survival signaling pathways, and protection by pre-miR-25 was abrogated by the p70S6k inhibitor rapamycin. Conclusions. MicroRNA-25 blocks corticosterone-induced VSMC apoptosis by targeting MOAP1 and the p70S6k pathway. Therapeutic manipulation of miR-25 may reduce atherosclerosis and unstable plaque formation associated with chronic stress.

Original languageEnglish (US)
Article number2691514
JournalOxidative Medicine and Cellular Longevity
Volume2019
DOIs
StatePublished - Jan 1 2019

Fingerprint

Corticosterone
MicroRNAs
Smooth Muscle Myocytes
Muscle
Cells
Apoptosis
Vascular Smooth Muscle
70-kDa Ribosomal Protein S6 Kinases
Cell death
Glucocorticoids
Atherosclerosis
Cell Death
Oxidative stress
Atherosclerotic Plaques
Sirolimus
Cellular Structures
Psychological Stress
Caspase 3
Heart Diseases

ASJC Scopus subject areas

  • Biochemistry
  • Aging
  • Cell Biology

Cite this

MicroRNA-25 protects smooth muscle cells against corticosterone-induced apoptosis. / Zhang, Bin; Zhang, Gaoxing; Wei, Tianlu; Yang, Zhen; Tan, Wenfeng; Mo, Ziqing; Liu, Jinxue; Li, Dong; Wei, Yidong; Zhang, Lukun; Webster, Keith A.; Wei, Jianqin.

In: Oxidative Medicine and Cellular Longevity, Vol. 2019, 2691514, 01.01.2019.

Research output: Contribution to journalArticle

Zhang, B, Zhang, G, Wei, T, Yang, Z, Tan, W, Mo, Z, Liu, J, Li, D, Wei, Y, Zhang, L, Webster, KA & Wei, J 2019, 'MicroRNA-25 protects smooth muscle cells against corticosterone-induced apoptosis', Oxidative Medicine and Cellular Longevity, vol. 2019, 2691514. https://doi.org/10.1155/2019/2691514
Zhang, Bin ; Zhang, Gaoxing ; Wei, Tianlu ; Yang, Zhen ; Tan, Wenfeng ; Mo, Ziqing ; Liu, Jinxue ; Li, Dong ; Wei, Yidong ; Zhang, Lukun ; Webster, Keith A. ; Wei, Jianqin. / MicroRNA-25 protects smooth muscle cells against corticosterone-induced apoptosis. In: Oxidative Medicine and Cellular Longevity. 2019 ; Vol. 2019.
@article{e7eab2e81f9b4fd3844f3c4093feffac,
title = "MicroRNA-25 protects smooth muscle cells against corticosterone-induced apoptosis",
abstract = "Background and Aims. Vascular smooth muscle cells (VSMCs) are central components of atherosclerotic plaque. Loss of VSMCs through apoptotic cell death can cause fibrous cap thinning, necrotic core formation, and calcification that may destabilize plaque. Elevated glucocorticoid levels caused by psychological stress promote VSMC apoptosis and can exacerbate atherosclerosis in mice and humans. Changes in the levels of antiapoptosis microRNA-25 (miR-25) have been linked with heart disease, inflammation, VSMC phenotype, oxidative stress, and apoptosis. Here, we investigated the pathways and mechanisms of glucocorticoid-induced apoptosis of mouse VSMCs and the protective role of miR-25. Methods. Primary mouse VSMCs were cultured +/- corticosterone for 48 h. Apoptosis, ROS, apoptotic protein activities, miR-25, MOAP1, a miR-25 target, and p70S6 kinase were quantified at intervals. The roles of miR-25 were assessed by treating cells with lenti-pre-miR-25 and anti-miR-25. Results. VSMC apoptosis, caspase-3 activity, and Bax were increased by corticosterone, and cell death was paralleled by marked loss of miR-25. Protection was conferred by pre-miR-25 and exacerbated by anti-miR-25. Pre-miR-25 conferred reduced expression of the proapoptotic protein MOAP1, and the protective effects of pre-miR-25 were abrogated by overexpressing MOAP1. The antiapoptotic effects of miR-25 were paralleled by inhibition of the p70S6K pathway, a convergence target for the survival signaling pathways, and protection by pre-miR-25 was abrogated by the p70S6k inhibitor rapamycin. Conclusions. MicroRNA-25 blocks corticosterone-induced VSMC apoptosis by targeting MOAP1 and the p70S6k pathway. Therapeutic manipulation of miR-25 may reduce atherosclerosis and unstable plaque formation associated with chronic stress.",
author = "Bin Zhang and Gaoxing Zhang and Tianlu Wei and Zhen Yang and Wenfeng Tan and Ziqing Mo and Jinxue Liu and Dong Li and Yidong Wei and Lukun Zhang and Webster, {Keith A.} and Jianqin Wei",
year = "2019",
month = "1",
day = "1",
doi = "10.1155/2019/2691514",
language = "English (US)",
volume = "2019",
journal = "Oxidative Medicine and Cellular Longevity",
issn = "1942-0900",
publisher = "Hindawi Publishing Corporation",

}

TY - JOUR

T1 - MicroRNA-25 protects smooth muscle cells against corticosterone-induced apoptosis

AU - Zhang, Bin

AU - Zhang, Gaoxing

AU - Wei, Tianlu

AU - Yang, Zhen

AU - Tan, Wenfeng

AU - Mo, Ziqing

AU - Liu, Jinxue

AU - Li, Dong

AU - Wei, Yidong

AU - Zhang, Lukun

AU - Webster, Keith A.

AU - Wei, Jianqin

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background and Aims. Vascular smooth muscle cells (VSMCs) are central components of atherosclerotic plaque. Loss of VSMCs through apoptotic cell death can cause fibrous cap thinning, necrotic core formation, and calcification that may destabilize plaque. Elevated glucocorticoid levels caused by psychological stress promote VSMC apoptosis and can exacerbate atherosclerosis in mice and humans. Changes in the levels of antiapoptosis microRNA-25 (miR-25) have been linked with heart disease, inflammation, VSMC phenotype, oxidative stress, and apoptosis. Here, we investigated the pathways and mechanisms of glucocorticoid-induced apoptosis of mouse VSMCs and the protective role of miR-25. Methods. Primary mouse VSMCs were cultured +/- corticosterone for 48 h. Apoptosis, ROS, apoptotic protein activities, miR-25, MOAP1, a miR-25 target, and p70S6 kinase were quantified at intervals. The roles of miR-25 were assessed by treating cells with lenti-pre-miR-25 and anti-miR-25. Results. VSMC apoptosis, caspase-3 activity, and Bax were increased by corticosterone, and cell death was paralleled by marked loss of miR-25. Protection was conferred by pre-miR-25 and exacerbated by anti-miR-25. Pre-miR-25 conferred reduced expression of the proapoptotic protein MOAP1, and the protective effects of pre-miR-25 were abrogated by overexpressing MOAP1. The antiapoptotic effects of miR-25 were paralleled by inhibition of the p70S6K pathway, a convergence target for the survival signaling pathways, and protection by pre-miR-25 was abrogated by the p70S6k inhibitor rapamycin. Conclusions. MicroRNA-25 blocks corticosterone-induced VSMC apoptosis by targeting MOAP1 and the p70S6k pathway. Therapeutic manipulation of miR-25 may reduce atherosclerosis and unstable plaque formation associated with chronic stress.

AB - Background and Aims. Vascular smooth muscle cells (VSMCs) are central components of atherosclerotic plaque. Loss of VSMCs through apoptotic cell death can cause fibrous cap thinning, necrotic core formation, and calcification that may destabilize plaque. Elevated glucocorticoid levels caused by psychological stress promote VSMC apoptosis and can exacerbate atherosclerosis in mice and humans. Changes in the levels of antiapoptosis microRNA-25 (miR-25) have been linked with heart disease, inflammation, VSMC phenotype, oxidative stress, and apoptosis. Here, we investigated the pathways and mechanisms of glucocorticoid-induced apoptosis of mouse VSMCs and the protective role of miR-25. Methods. Primary mouse VSMCs were cultured +/- corticosterone for 48 h. Apoptosis, ROS, apoptotic protein activities, miR-25, MOAP1, a miR-25 target, and p70S6 kinase were quantified at intervals. The roles of miR-25 were assessed by treating cells with lenti-pre-miR-25 and anti-miR-25. Results. VSMC apoptosis, caspase-3 activity, and Bax were increased by corticosterone, and cell death was paralleled by marked loss of miR-25. Protection was conferred by pre-miR-25 and exacerbated by anti-miR-25. Pre-miR-25 conferred reduced expression of the proapoptotic protein MOAP1, and the protective effects of pre-miR-25 were abrogated by overexpressing MOAP1. The antiapoptotic effects of miR-25 were paralleled by inhibition of the p70S6K pathway, a convergence target for the survival signaling pathways, and protection by pre-miR-25 was abrogated by the p70S6k inhibitor rapamycin. Conclusions. MicroRNA-25 blocks corticosterone-induced VSMC apoptosis by targeting MOAP1 and the p70S6k pathway. Therapeutic manipulation of miR-25 may reduce atherosclerosis and unstable plaque formation associated with chronic stress.

UR - http://www.scopus.com/inward/record.url?scp=85063450139&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85063450139&partnerID=8YFLogxK

U2 - 10.1155/2019/2691514

DO - 10.1155/2019/2691514

M3 - Article

C2 - 30992737

AN - SCOPUS:85063450139

VL - 2019

JO - Oxidative Medicine and Cellular Longevity

JF - Oxidative Medicine and Cellular Longevity

SN - 1942-0900

M1 - 2691514

ER -