MicroRNA expression profile of pulmonary artery smooth muscle cells and the effect of let-7d in chronic thromboembolic pulmonary hypertension

Lei Wang, Li Juan Guo, Jie Liu, Wang Wang, Jason X.J. Yuan, Lan Zhao, Jun Wang, Chen Wang

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening condition characterized by single or recurrent pulmonary thromboemboli, which promote pulmonary vascular remodeling. MicroRNA (miRNA), is a small, noncoding RNA that is involved in multiple cell processes and functions and may participate in the pathogenesis of CTEPH. Our aims were to identify the miRNA expression signature in pulmonary artery smooth muscle cells (PASMCs) of CTEPH patients and to study the role of let-7d in CTEPH pathogenesis. The miRNA expression profile was analyzed by microarray in PASMCs of CTEPH and control patients. Differentially expressed miRNAs were selectively validated by stem-loop quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR). The role of let-7d was identified by in silico analysis, and its effect on the proliferation of PASMCs was measured by methyl thiazolyl tetrazolium (MTT). Student’s unpaired t test, the Fisher exact test, and the χ2test were used for statistical analysis. Eighteen miRNAs were differentially expressed in PASMCs from CTEPH patients, including 12 upregulated miRNAs and 6 downregulated miRNAs; among the latter, let-7d decreased 0.58-fold in CTEPH patients, as validated by qRT-PCR. It was found that let-7d could inhibit the proliferation of PASMCs through upregulation of p21. In conclusion, PASMCs in CTEPH patients have an aberrant miRNA profile and reduced let-7d, which could promote PASMC proliferation and may be involved in the pathogenesis of CTEPH.

Original languageEnglish (US)
Pages (from-to)654-664
Number of pages11
JournalPulmonary Circulation
Volume3
Issue number3
DOIs
StatePublished - Sep 2013
Externally publishedYes

Keywords

  • Chronic thromboembolic pulmonary hypertension
  • Let-7d
  • Proliferation
  • Pulmonary artery smooth muscle cell

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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