TY - JOUR
T1 - MicroRNA expression profile of pulmonary artery smooth muscle cells and the effect of let-7d in chronic thromboembolic pulmonary hypertension
AU - Wang, Lei
AU - Guo, Li Juan
AU - Liu, Jie
AU - Wang, Wang
AU - Yuan, Jason X.J.
AU - Zhao, Lan
AU - Wang, Jun
AU - Wang, Chen
N1 - Funding Information:
Source of Support: Fund of China 973 program (2009CB522107) and National Natural Science Foundation of China (3081010394, 810700742, 81111130212, 81228001).
PY - 2013/9
Y1 - 2013/9
N2 - 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.
AB - 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.
KW - Chronic thromboembolic pulmonary hypertension
KW - Let-7d
KW - Proliferation
KW - Pulmonary artery smooth muscle cell
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U2 - 10.1086/674310
DO - 10.1086/674310
M3 - Article
AN - SCOPUS:84903591380
VL - 3
SP - 654
EP - 664
JO - Pulmonary Circulation
JF - Pulmonary Circulation
SN - 2045-8932
IS - 3
ER -