There is growing evidence that microRNAs are implicated in pulmonary arterial hypertension (PAH), but underlying mechanisms remain elusive. In a recent study led by researchers from Shenzhen University, scientists used miRNA microarray services to identify that miR-223 was significantly downregulated in chronically hypoxic mouse and rat lungs, as well as in pulmonary artery and pulmonary artery smooth muscle cells (PASMC) exposed to hypoxia.
Their study showed that knockdown of miR-223 increased PASMC proliferation. In contrast, miR-223 overexpression abrogated cell proliferation, migration and stress fiber formation. Administering miR-223 agomir in vivo antagonized hypoxia-induced increase in pulmonary artery pressure and distal arteriole muscularization. RhoB, which was increased by hypoxia, was identified as one of the targets of miR-223. Additionally, overexpressed miR-223 suppressed RhoB and inhibited the consequent phosphorylation of myosin phosphatase target subunit (MYPT1) and the expression of myosin light chain of myosin II (MLC2), which was identified as another target of miR-223. Furthermore, serum miR-223 levels were decreased in female patients with PAH associated with congenital heart disease.
Rat and human PASMC were transfected with mimic control (miR-Con) or miR-223 mimic (miR-223) and exposed to hypoxia (3% O2) or normoxia for 24 h in triplicate. Cell proliferation was determined by EdU incorporation assay (A) and PCNA immunoblotting (B). Data are shown as means ± SE (n = 3). (C) Transwell migration assay showing the migration of rPASMC or hPASMC with miR-223 overexpression. Bar charts representing relative migrated cells after 24 h. Data (mean ± SE) is derived from an average of three independent experiments, with five visual fields in triplicate samples. (D) F-actin in cells was stained with TRITC-phalloidin and visualized by confocal microscopy. *p < 0.05, **p < 0.01.
This study provides the first evidence that miR-223 can regulate PASMC proliferation, migration, and actomyosin reorganization through its novel targets, RhoB and MLC2, resulting in vascular remodeling and the development of PAH. It also highlights miR-223 as a potential circulating biomarker and a small molecule drug for diagnosis and treatment of PAH.
miRNA Microarray Service – LC Sciences provides a microRNA (miRNA) expression profiling service using microarrays based on our in-house developed µParaflo® technology platform. We have standard arrays for all mature miRNAs of all species available in the latest version of the miRBase database (Release 21, July 2014). Our service is comprehensive and includes sample labeling, array hybridization, image data processing and in-depth data analysis. Two-three weeks after receiving your total RNA samples, we’ll send you both the raw and fully analyzed data. [Learn more…]
Y. Zeng, X. Zhang, K. Kang, J. Chen, Z. Wu, J. Huang, W. Lu, Y. Chen, J. Zhang, Z. Wang, Y. Zhai, J. Qu, R. Ramchandran, J. U. Raj, J. Wang, D. Gou (2016) MicroRNA-223 Attenuates Hypoxia-induced Vascular Remodeling by Targeting RhoB/MLC2 in Pulmonary Arterial Smooth Muscle Cells Scientific Reports 6: 24900; doi: 10.1038/srep24900 [article]