Abstract
Hypoxia-induced pulmonary hypertension (PH), which is characterized by vascular remodeling of blood vessels, is a significant complication of chronic obstructive pulmonary disease (COPD). In this study, we screened 13 candidate miRNAs in pulmonary artery smooth muscle cells (PASMCs) harvested from COPD patients with PH (n = 18) and normal controls (n = 15) and found that the expression of miR-214 was differentially expressed between these two groups. Additionally, cyclin L2 (CCNL2) was validated as a target of miR-214 in PASMCs using a luciferase assay. Based on real-time PCR, immunohistochemistry and western blot, the expression of CCNL2 was substantially downregulated in PASMCs from COPD patients with PH compared with those from normal controls. Moreover, the relationship between miRNA and mRNA expression was confirmed using real-time PCR and western blot in PASMCs transfected with miR-214 mimics. Furthermore, the introduction of miR-214 significantly promoted the proliferation of PASMCs by suppressing cell apoptosis, and this effect was mediated by the downregulation of CCNL2. Exposure of PASMCs to hypoxia significantly increased the expression of miR-214, decreased the expression of CCNL2, and promoted cell proliferation. However, these effects were significantly attenuated by the introduction of miR-214 inhibitors, which significantly downregulated miR-214 expression and upregulated CCNL2 expression.
Highlights
Pulmonary hypertension (PH) is a serious and occasionally fatal medical condition that is characterized by vasoconstriction and vascular remodeling, resulting in increased vascular resistance and right ventricular dysfunction[1]
The expression level of miR-214 is significantly upregulated in human pulmonary artery smooth muscle cells (PASMCs) harvested from chronic obstructive pulmonary disease (COPD) patients with pulmonary hypertension (PH) compared to hPASMCs harvested from COPD patients without PH
To identify the miRNA that is responsible for the development of hypoxia-induced PH, such as PH in patients with COPD, we quantified the expression levels of thirteen candidate miRNAs that have been reported to be associated with hypoxia in previous publications[12,14] and compared the expression patterns of those miRNAs in hPASMCs from COPD patients with and without PH
Summary
Pulmonary hypertension (PH) is a serious and occasionally fatal medical condition that is characterized by vasoconstriction and vascular remodeling, resulting in increased vascular resistance and right ventricular dysfunction[1]. As the major component of the vasculature, pulmonary artery smooth muscle cells (PASMCs) play an essential role in the response to hypoxia, and dysregulation of their activity is closely related to the development of PH. Recent studies of miRNAs demonstrated that these molecules may play substantial and important roles in the molecular mechanisms underlying the physiological and pathophysiological adaptations to hypoxia. Among miRNAs, those whose expression is dynamically altered by hypoxia are called “hypoxamiRs”11, and upregulation or downregulation of hypoxamiRs has been implicated in the development of hypoxia-induced PH, a major complication of COPD, by suppressing target gene expression or releasing the physiologic inhibition of the expression of certain genes[12]. To explore the role of candidate miRNAs in hypoxia-induced PH, we performed quantitative real-time PCR-based screening for differentially expressed miRNAs and identified miR-214 as the only significantly upregulated miRNA in PASMCs harvested from COPD patients with PH. The objectives of the current study were to determine whether differentially expressed miR-214 is responsible for the abnormally enhanced proliferation of PASMCs and to identify the molecular mechanism underlying the aberrant enhancement of PASMC proliferation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
