期刊
EXPERIMENTAL CELL RESEARCH
卷 359, 期 1, 页码 235-242出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2017.07.024
关键词
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资金
- Texas A & M Health Science Center, College of Medicine
- Scientist Development Grant [13SDG 914630018]
- Beijing Natural Science Foundation [7152083]
- [0835227N]
Pulmonary arterial hypertension (PAH) is a progressive pulmonary vascular disease which is associated with pulmonary arterial endothelial cells (PAEC) dysfunction and pulmonary arterial smooth muscle cells proliferation. Moreover, inflammation is contributing a critical role in EC dysfunction and remains elusive. Nuclear factor-kappa B (NF-kappa B) is a master transcriptional regulator in various cardiovascular pathologies; but, NF-kappa B's role in EC dysfunction in unknown. Our previous study using cardiac and lung specific I kappa B alpha mutant mice (3 M and IKBM) showed that PAH induced right ventricular hypertrophy (RVH) was prevented in monocrotaline (MCT) treated 3 M and IKBM mice, compared to the wild-type mice. Recently, microRNAs (miRNAs) have emerged as a new class of post-transcriptional regulators in vascular remodeling; but, NF-kappa B regulated miRNA modulation in EC dysfunction is unknown. Using miRNA array analysis, we identified mi-130a which is upregulated in MCT-induced PAH mouse model, as a possible candidate to study. We showed that overexpressing miR-130a in lung microvascular endothelial cells (MVEC) promoted activation of alpha-smooth muscle actin, a critical component in endothelial-to-mesenchymal transition in EC remodeling. In this study, we demonstrated that bone morphogenetic protein receptor 2 (BMPR2) was a target for miR-130a and miR-130a was regulated by NF-kappa B which controlled apoptosis and vascular genes in MVEC. The findings reveal that NF-kappa B -mediated miR-130a modulation is critical in lung vascular remodeling.
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