English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

BACKGROUND Pulmonary arterial hypertension (PAH) is a fatal disease characterized by impaired regulation of pulmonary artery vascular growth and remodeling. Aberrant expression of miR-17 has been shown to be involved in the pathogenesis of PAH, but its underlying molecular mechanism has not been elucidated. MATERIAL AND METHODS Mitofusin 2 (MFN2) expression was determined by qRT-PCR. The protein expression levels of MFN2, proliferating cell nuclear antigen (PCNA), and pro-apoptotic protein cleaved Caspase-3 were measured using Western blot analysis. Cell proliferation and apoptosis were assessed by CellTiter-Glo reagent and flow cytometry, respectively. Caspase-3/7 activity was measured using an Apo-ONE Homogeneous Caspase-3/7 assay kit. The regulation of miR-17 on MFN2 expression was assessed using luciferase reporter assay system. RESULTS miR-17 expression was upregulated in human pulmonary artery smooth muscle cells (hPASMCs) treated with hypoxia and lung tissues of PAH patients. Inhibition of miR-17 suppressed hypoxia-induced proliferation and promoted apoptosis in hPASMCs. miR-17 inhibited MFN2 expression by binding to its 3'-UTR. Decreased cell viability and increased apoptosis and Caspase-3 activity were observed in the anti-miR-17 + siNC group compared with the anti-miR-NC + siNC group. The expression of cleaved Caspase-3 was upregulated and the expression of PCNA was downregulated in the anti-miR-17 + siNC group. Moreover, these alterations were attenuated by knockdown of MFN2. CONCLUSIONS miR-17 regulates proliferation and apoptosis in hPASMCs through MFN2 modulation. We found that miR-17 acts as a potential regulator of proliferation and apoptosis of hPASMCs, and that it might be developed as a promising new strategy for the treatment of PAH.

Upregulated miR-17 Regulates Hypoxia-Mediated Human Pulmonary Artery Smooth Muscle Cell Proliferation and Apoptosis by Targeting Mitofusin 2