MicroRNA-15b/16 attenuates vascular neointima formation by promoting the contractile phenotype of vascular smooth muscle through targeting YAP

Fei Xu, Abu Shufian Ishtiaq Ahmed, Xiuhua Kang, Guoqing Hu, Fang Liu, Wei Zhang, Jiliang Zhou

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Objective.To investigate the functional role of the microRNA (miR)-15b/16 in vascular smooth muscle (SM) phenotypic modulation. Approach and Results.We found that miR-15b/16 is one of the most abundant mRs expressed in contractile vascular smooth muscle cells (VSMCs). However, when contractile VSMCs get converted to a synthetic phenotype, miR-15b/16 expression is significantly reduced. Knocking down endogenous miR-15b/16 in VSMCs attenuates SM-specific gene expression but promotes VSMC proliferation and migration. Conversely, overexpression of miR-15b/16 promotes SM contractile gene expression while attenuating VSMC migration and proliferation. Consistent with this, overexpression of miR-15b/16 in a rat carotid balloon injury model markedly attenuates injury-induced SM dedifferentiation and neointima formation. Mechanistically, we identified the potent oncoprotein yes-associated protein (YAP) as a downstream target of miR-15b/16 in VSMCs. Reporter assays validated that miR-15b/16 targets YAP'fs 3'Πuntranslated region. Moreover, overexpression of miR-15b/16 significantly represses YAP expression, whereas conversely, depletion of endogenous miR-15b/16 results in upregulation of YAP expression. Conclusions.These results indicate that miR-15b/16 plays a critical role in SM phenotypic modulation at least partly through targeting YAP. Restoring expression of miR-15b/16 would be a potential therapeutic approach for treatment of proliferative vascular diseases.

Original languageEnglish (US)
Pages (from-to)2145-2152
Number of pages8
JournalArteriosclerosis, thrombosis, and vascular biology
Volume35
Issue number10
DOIs
StatePublished - Oct 25 2015

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Neointima
MicroRNAs
Vascular Smooth Muscle
Blood Vessels
Phenotype
Smooth Muscle Myocytes
Proteins
Smooth Muscle
Cell Movement
Cell Proliferation
Gene Expression
Oncogene Proteins
Wounds and Injuries
3' Untranslated Regions
Vascular Diseases
Up-Regulation

Keywords

  • Neointima formation
  • Phenotypic modulation
  • Smooth muscle
  • YAP
  • microRNA

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

MicroRNA-15b/16 attenuates vascular neointima formation by promoting the contractile phenotype of vascular smooth muscle through targeting YAP. / Xu, Fei; Ahmed, Abu Shufian Ishtiaq; Kang, Xiuhua; Hu, Guoqing; Liu, Fang; Zhang, Wei; Zhou, Jiliang.

In: Arteriosclerosis, thrombosis, and vascular biology, Vol. 35, No. 10, 25.10.2015, p. 2145-2152.

Research output: Contribution to journalArticle

Xu, Fei ; Ahmed, Abu Shufian Ishtiaq ; Kang, Xiuhua ; Hu, Guoqing ; Liu, Fang ; Zhang, Wei ; Zhou, Jiliang. / MicroRNA-15b/16 attenuates vascular neointima formation by promoting the contractile phenotype of vascular smooth muscle through targeting YAP. In: Arteriosclerosis, thrombosis, and vascular biology. 2015 ; Vol. 35, No. 10. pp. 2145-2152.
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abstract = "Objective.To investigate the functional role of the microRNA (miR)-15b/16 in vascular smooth muscle (SM) phenotypic modulation. Approach and Results.We found that miR-15b/16 is one of the most abundant mRs expressed in contractile vascular smooth muscle cells (VSMCs). However, when contractile VSMCs get converted to a synthetic phenotype, miR-15b/16 expression is significantly reduced. Knocking down endogenous miR-15b/16 in VSMCs attenuates SM-specific gene expression but promotes VSMC proliferation and migration. Conversely, overexpression of miR-15b/16 promotes SM contractile gene expression while attenuating VSMC migration and proliferation. Consistent with this, overexpression of miR-15b/16 in a rat carotid balloon injury model markedly attenuates injury-induced SM dedifferentiation and neointima formation. Mechanistically, we identified the potent oncoprotein yes-associated protein (YAP) as a downstream target of miR-15b/16 in VSMCs. Reporter assays validated that miR-15b/16 targets YAP'fs 3'Πuntranslated region. Moreover, overexpression of miR-15b/16 significantly represses YAP expression, whereas conversely, depletion of endogenous miR-15b/16 results in upregulation of YAP expression. Conclusions.These results indicate that miR-15b/16 plays a critical role in SM phenotypic modulation at least partly through targeting YAP. Restoring expression of miR-15b/16 would be a potential therapeutic approach for treatment of proliferative vascular diseases.",
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AU - Hu, Guoqing

AU - Liu, Fang

AU - Zhang, Wei

AU - Zhou, Jiliang

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N2 - Objective.To investigate the functional role of the microRNA (miR)-15b/16 in vascular smooth muscle (SM) phenotypic modulation. Approach and Results.We found that miR-15b/16 is one of the most abundant mRs expressed in contractile vascular smooth muscle cells (VSMCs). However, when contractile VSMCs get converted to a synthetic phenotype, miR-15b/16 expression is significantly reduced. Knocking down endogenous miR-15b/16 in VSMCs attenuates SM-specific gene expression but promotes VSMC proliferation and migration. Conversely, overexpression of miR-15b/16 promotes SM contractile gene expression while attenuating VSMC migration and proliferation. Consistent with this, overexpression of miR-15b/16 in a rat carotid balloon injury model markedly attenuates injury-induced SM dedifferentiation and neointima formation. Mechanistically, we identified the potent oncoprotein yes-associated protein (YAP) as a downstream target of miR-15b/16 in VSMCs. Reporter assays validated that miR-15b/16 targets YAP'fs 3'Πuntranslated region. Moreover, overexpression of miR-15b/16 significantly represses YAP expression, whereas conversely, depletion of endogenous miR-15b/16 results in upregulation of YAP expression. Conclusions.These results indicate that miR-15b/16 plays a critical role in SM phenotypic modulation at least partly through targeting YAP. Restoring expression of miR-15b/16 would be a potential therapeutic approach for treatment of proliferative vascular diseases.

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