MicroRNA‑153 attenuates hypoxia‑induced excessive proliferation and migration of pulmonary arterial smooth muscle cells by targeting ROCK1 and NFATc3

Abstract

The aim of the present study was to explore the effect of microRNA (miR)-153 on the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) in a hypoxic condition by targeting ρ-associated, coiled-coil-containing protein kinase 1 (ROCK1) and nuclear factor of activated T cells cytoplasmic 3 (NFATc3). The right ventricular systolic pressure, right ventricular hypertrophy index, medial wall thickness and medial wall area were studied at different time-points after rats were exposed to hypoxia. Western blot analysis was used to detect ROCK1 and NFATc3 protein levels. In addition, reverse transcription-quantitative (RT-q) PCR was performed to confirm the mRNA levels of miR-153, ROCK1 and NFATc3 in human (H)PASMCs under hypoxic conditions. Transfected cells were then used to evaluate the effect of miR-153 on cell proliferation and migration abilities. The association between miR-153 and ROCK1 or NFATc3 was identified through double luciferase assays. Hypoxia induced pulmonary vascular remodeling and pulmonary arterial hypertension, which resulted from the abnormal proliferation of HPASMCs. ROCK1 and NFATc3 were the target genes of miR-153 and miR-153 mimic inhibited the protein expressions of ROCK1 and NFATc3 in HPASMCs and further inhibited cell proliferation and migration under hypoxic conditions. By contrast, the miR-153 inhibitor promoted the proliferation and migration of HPASMCs. miR-153 regulated the proliferation and migration of HPASMCs under hypoxia by targeting ROCK1 and NFATc3.

Single-Cell RNA Sequencing Reveals Novel Genes Regulated by Hypoxia in the Lung Vasculature

“…3a). Hypoxia increased Cd146, Rgs4, Rgs5, Nox4 , and Rock1 expression in smooth muscle cells [37-40], with Wt and Notch3 -Null cells exhibiting similar profiles (Fig. 3a) [37, 41-43].…”

Transcriptional and Epigenetic Factors Associated with Early Thrombosis of Femoral Artery Involved in Arteriovenous Fistula

“…The levels of miR-34a-5p, associated with atherosclerosis and miR-34a-5p, play a crucial role in inflammatory pathology [ 67 ] and various studies [ 68 , 69 ] have discussed miR-34a-5p, which was found to be inhibited in this study, as a potential therapeutic target in cardiovascular disease. miR-205-5p, which was found to be activated in this study, suppresses the proliferation of pulmonary VSMCs [ 70 ], whereas miR-153, which was found to be inhibited in this study, attenuates hypoxia-induced excessive proliferation and migration of pulmonary arterial SMCs [ 71 ]. miR-22, which was found to be inhibited in this study, regulates VSMCs apoptosis (through p38MAPKα) and vascular remodeling in aortic dissection [ 72 ], whereas miR-219, which was found to be inhibited in this study, is associated with vascular ischemia during cerebral artery occlusion [ 73 ] ( Table 1 and Table 2 ).…”

Circ_0026466 Knockdown Protects Human Bronchial Epithelial Cells From Cigarette Smoke Extract–induced Injury by Promoting the Mir-153-3p/Traf6/Nf-Κb Pathway

“…COPD occurrence is also associated with aberrant miRNA expression (14). A former study reported that miR-153-3p repressed hypoxia-caused PASMC proliferation and migration in a pulmonary arterial hypertension (PAH) cell model (15). Moreover, miR-153-3p interacted with transforming growth factor beta receptor 2 to act an anti-fibrotic effect in pulmonary fibrosis (16).…”