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MicroRNA-140-5p targeting tumor necrosis factor-α prevents pulmonary arterial hypertension.

Abstract：

BACKGROUND:Pulmonary arterial hypertension (PAH) is characterized by the apoptosis resistance and hyperproliferation of pulmonary artery smooth muscle cells (PASMCs). Its pathogenesis has not been revealed. Here, we carried out experiments to investigate the functions of miR-140-5p and tumor necrosis factor-α (TNF-α). METHODS:We selected GSE703 from Gene Expression Omnibus (GEO) Database to conduct microarray analysis using R software and Gene Set Enrichment Analysis (GSEA). Combing bioinformatics results, the upregulation of miR-140-5p inhibited PAH progression through targeting TNF-α. RNA expression was measured by quantitative real-time polymerase chain reaction (RT-qPCR) and protein level was measured by western blot analysis and enzyme-linked immunosorbent assays (ELISA). We conducted monocrotaline (MCT) injection to rats to form PAH animal models. The lung tissues were observed by hematoxylin-eosin (HE) staining and Sirius red-picric acid staining. Right ventricular systolic pressure (RVSP) and the ratio of right ventricle (RV)-to-left ventricle (LV) plus septum (S) weight (RV/[LV + S]) were measured in MCT-induced animal models. Overexpression of miR-140-5p and TNF-α were utilized to research the proliferation, migration, and phenotypic variation of hypoxia-mediated PASMCs. The binding between miR-140-5p and TNF-α 3'-untranslated region (3'-UTR) was confirmed via luciferase reporter assay. RESULTS:Downregulation of miR-140-5p and upregulation of TNF-α were observed in PAH rat model and hypoxia-mediated PASMCs. And we proved that overexpression of miR-140-5p could suppress the proliferation, migration, and phenotypic variation of PASMCs, therefore inhibiting PAH pathogenesis. Luciferase assay verified that miR-140-5p targeted TNF-α directly. A converse correlation was also shown between miR-140-5p and TNF-α in PASMCs. CONCLUSIONS:miR-140-5p and TNF-α are important regulators in PAH pathology and may serve as a therapeutic target for PAH.

journal_name

J Cell Physiol

journal_title

Journal of cellular physiology

authors

Zhu TT,Zhang WF,Yin YL,Liu YH,Song P,Xu J,Zhang MX,Li P

doi

10.1002/jcp.27642

subject

Has Abstract

pub_date

2019-06-01 00:00:00

pages

9535-9550

issue

eissn

0021-9541

issn

1097-4652

journal_volume

234

pub_type

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MicroRNA-140-5p targeting tumor necrosis factor-α prevents pulmonary arterial hypertension.