MicroRNA-10A* and MicroRNA-21 modulate endothelial progenitor cell senescence via suppressing high-mobility group A2.

Shoukang Zhu, Shanming Deng, Q. Ma, Taifang Zhang, Chunling Jia, Degen Zhuo, Falin Yang, Jianqin Wei, Liyong Wang, Derek M Dykxhoorn, Joshua Hare, Pascal Goldschmidt-Clermont, Chunming Dong

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

Endothelial progenitor cells (EPCs) contribute to the regeneration of endothelium. Aging-associated senescence results in reduced number and function of EPCs, potentially contributing to increased cardiac risk, reduced angiogenic capacity, and impaired cardiac repair effectiveness. The mechanisms underlying EPC senescence are unknown. Increasing evidence supports the role of microRNAs in regulating cellular senescence. We aimed to determine whether microRNAs regulated EPC senescence and, if so, what the underlying mechanisms are. To map the microRNA/gene expression signatures of EPC senescence, we performed microRNA profiling and microarray analysis in lineage-negative bone marrow cells from young and aged wild-type and apolipoprotein E-deficient mice. We identified 2 microRNAs, microRNA-10A* (miR-10A*), and miR-21, and their common target gene Hmga2 as critical regulators for EPC senescence. Overexpression of miR-10A* and miR-21 in young EPCs suppressed Hmga2 expression, caused EPC senescence, as evidenced by senescence-associated β-galactosidase upregulation, decreased self-renewal potential, increased p16(Ink4a)/p19(Arf) expression, and resulted in impaired EPC angiogenesis in vitro and in vivo, resembling EPCs derived from aged mice. In contrast, suppression of miR-10A* and miR-21 in aged EPCs increased Hmga2 expression, rejuvenated EPCs, resulting in decreased senescence-associated β-galactosidase expression, increased self-renewal potential, decreased p16(Ink4a)/p19(Arf) expression, and improved EPC angiogenesis in vitro and in vivo. Importantly, these phenotypic changes were rescued by miRNA-resistant Hmga2 cDNA overexpression. miR-10A* and miR-21 regulate EPC senescence via suppressing Hmga2 expression and modulation of microRNAs may represent a potential therapeutic intervention in improving EPC-mediated angiogenesis and vascular repair.

Original languageEnglish (US)
Pages (from-to)152-164
Number of pages13
JournalUnknown Journal
Volume112
Issue number1
DOIs
StatePublished - 2013
Externally publishedYes

Fingerprint

Cell Aging
Endothelial cells
MicroRNAs
varespladib methyl
cells
angiogenesis
Galactosidases
Endothelial Progenitor Cells
mice
Repair
endothelium
bone marrow
gene expression
regulators
Apolipoproteins E
Microarray Analysis
Microarrays
regeneration
Transcriptome
Gene expression

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

MicroRNA-10A* and MicroRNA-21 modulate endothelial progenitor cell senescence via suppressing high-mobility group A2. / Zhu, Shoukang; Deng, Shanming; Ma, Q.; Zhang, Taifang; Jia, Chunling; Zhuo, Degen; Yang, Falin; Wei, Jianqin; Wang, Liyong; Dykxhoorn, Derek M; Hare, Joshua; Goldschmidt-Clermont, Pascal; Dong, Chunming.

In: Unknown Journal, Vol. 112, No. 1, 2013, p. 152-164.

Research output: Contribution to journalArticle

Zhu, Shoukang ; Deng, Shanming ; Ma, Q. ; Zhang, Taifang ; Jia, Chunling ; Zhuo, Degen ; Yang, Falin ; Wei, Jianqin ; Wang, Liyong ; Dykxhoorn, Derek M ; Hare, Joshua ; Goldschmidt-Clermont, Pascal ; Dong, Chunming. / MicroRNA-10A* and MicroRNA-21 modulate endothelial progenitor cell senescence via suppressing high-mobility group A2. In: Unknown Journal. 2013 ; Vol. 112, No. 1. pp. 152-164.
@article{d0cbd1595ff4431b9371c60e1c87d497,
title = "MicroRNA-10A* and MicroRNA-21 modulate endothelial progenitor cell senescence via suppressing high-mobility group A2.",
abstract = "Endothelial progenitor cells (EPCs) contribute to the regeneration of endothelium. Aging-associated senescence results in reduced number and function of EPCs, potentially contributing to increased cardiac risk, reduced angiogenic capacity, and impaired cardiac repair effectiveness. The mechanisms underlying EPC senescence are unknown. Increasing evidence supports the role of microRNAs in regulating cellular senescence. We aimed to determine whether microRNAs regulated EPC senescence and, if so, what the underlying mechanisms are. To map the microRNA/gene expression signatures of EPC senescence, we performed microRNA profiling and microarray analysis in lineage-negative bone marrow cells from young and aged wild-type and apolipoprotein E-deficient mice. We identified 2 microRNAs, microRNA-10A* (miR-10A*), and miR-21, and their common target gene Hmga2 as critical regulators for EPC senescence. Overexpression of miR-10A* and miR-21 in young EPCs suppressed Hmga2 expression, caused EPC senescence, as evidenced by senescence-associated β-galactosidase upregulation, decreased self-renewal potential, increased p16(Ink4a)/p19(Arf) expression, and resulted in impaired EPC angiogenesis in vitro and in vivo, resembling EPCs derived from aged mice. In contrast, suppression of miR-10A* and miR-21 in aged EPCs increased Hmga2 expression, rejuvenated EPCs, resulting in decreased senescence-associated β-galactosidase expression, increased self-renewal potential, decreased p16(Ink4a)/p19(Arf) expression, and improved EPC angiogenesis in vitro and in vivo. Importantly, these phenotypic changes were rescued by miRNA-resistant Hmga2 cDNA overexpression. miR-10A* and miR-21 regulate EPC senescence via suppressing Hmga2 expression and modulation of microRNAs may represent a potential therapeutic intervention in improving EPC-mediated angiogenesis and vascular repair.",
author = "Shoukang Zhu and Shanming Deng and Q. Ma and Taifang Zhang and Chunling Jia and Degen Zhuo and Falin Yang and Jianqin Wei and Liyong Wang and Dykxhoorn, {Derek M} and Joshua Hare and Pascal Goldschmidt-Clermont and Chunming Dong",
year = "2013",
doi = "10.1161/CIRCRESAHA.112.280016",
language = "English (US)",
volume = "112",
pages = "152--164",
journal = "Scientific Computing and Instrumentation",
issn = "1078-8956",
publisher = "Springer Wien",
number = "1",

}

TY - JOUR

T1 - MicroRNA-10A* and MicroRNA-21 modulate endothelial progenitor cell senescence via suppressing high-mobility group A2.

AU - Zhu, Shoukang

AU - Deng, Shanming

AU - Ma, Q.

AU - Zhang, Taifang

AU - Jia, Chunling

AU - Zhuo, Degen

AU - Yang, Falin

AU - Wei, Jianqin

AU - Wang, Liyong

AU - Dykxhoorn, Derek M

AU - Hare, Joshua

AU - Goldschmidt-Clermont, Pascal

AU - Dong, Chunming

PY - 2013

Y1 - 2013

N2 - Endothelial progenitor cells (EPCs) contribute to the regeneration of endothelium. Aging-associated senescence results in reduced number and function of EPCs, potentially contributing to increased cardiac risk, reduced angiogenic capacity, and impaired cardiac repair effectiveness. The mechanisms underlying EPC senescence are unknown. Increasing evidence supports the role of microRNAs in regulating cellular senescence. We aimed to determine whether microRNAs regulated EPC senescence and, if so, what the underlying mechanisms are. To map the microRNA/gene expression signatures of EPC senescence, we performed microRNA profiling and microarray analysis in lineage-negative bone marrow cells from young and aged wild-type and apolipoprotein E-deficient mice. We identified 2 microRNAs, microRNA-10A* (miR-10A*), and miR-21, and their common target gene Hmga2 as critical regulators for EPC senescence. Overexpression of miR-10A* and miR-21 in young EPCs suppressed Hmga2 expression, caused EPC senescence, as evidenced by senescence-associated β-galactosidase upregulation, decreased self-renewal potential, increased p16(Ink4a)/p19(Arf) expression, and resulted in impaired EPC angiogenesis in vitro and in vivo, resembling EPCs derived from aged mice. In contrast, suppression of miR-10A* and miR-21 in aged EPCs increased Hmga2 expression, rejuvenated EPCs, resulting in decreased senescence-associated β-galactosidase expression, increased self-renewal potential, decreased p16(Ink4a)/p19(Arf) expression, and improved EPC angiogenesis in vitro and in vivo. Importantly, these phenotypic changes were rescued by miRNA-resistant Hmga2 cDNA overexpression. miR-10A* and miR-21 regulate EPC senescence via suppressing Hmga2 expression and modulation of microRNAs may represent a potential therapeutic intervention in improving EPC-mediated angiogenesis and vascular repair.

AB - Endothelial progenitor cells (EPCs) contribute to the regeneration of endothelium. Aging-associated senescence results in reduced number and function of EPCs, potentially contributing to increased cardiac risk, reduced angiogenic capacity, and impaired cardiac repair effectiveness. The mechanisms underlying EPC senescence are unknown. Increasing evidence supports the role of microRNAs in regulating cellular senescence. We aimed to determine whether microRNAs regulated EPC senescence and, if so, what the underlying mechanisms are. To map the microRNA/gene expression signatures of EPC senescence, we performed microRNA profiling and microarray analysis in lineage-negative bone marrow cells from young and aged wild-type and apolipoprotein E-deficient mice. We identified 2 microRNAs, microRNA-10A* (miR-10A*), and miR-21, and their common target gene Hmga2 as critical regulators for EPC senescence. Overexpression of miR-10A* and miR-21 in young EPCs suppressed Hmga2 expression, caused EPC senescence, as evidenced by senescence-associated β-galactosidase upregulation, decreased self-renewal potential, increased p16(Ink4a)/p19(Arf) expression, and resulted in impaired EPC angiogenesis in vitro and in vivo, resembling EPCs derived from aged mice. In contrast, suppression of miR-10A* and miR-21 in aged EPCs increased Hmga2 expression, rejuvenated EPCs, resulting in decreased senescence-associated β-galactosidase expression, increased self-renewal potential, decreased p16(Ink4a)/p19(Arf) expression, and improved EPC angiogenesis in vitro and in vivo. Importantly, these phenotypic changes were rescued by miRNA-resistant Hmga2 cDNA overexpression. miR-10A* and miR-21 regulate EPC senescence via suppressing Hmga2 expression and modulation of microRNAs may represent a potential therapeutic intervention in improving EPC-mediated angiogenesis and vascular repair.

UR - http://www.scopus.com/inward/record.url?scp=85027935902&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85027935902&partnerID=8YFLogxK

U2 - 10.1161/CIRCRESAHA.112.280016

DO - 10.1161/CIRCRESAHA.112.280016

M3 - Article

VL - 112

SP - 152

EP - 164

JO - Scientific Computing and Instrumentation

JF - Scientific Computing and Instrumentation

SN - 1078-8956

IS - 1

ER -