miR-760 mediates hypoxia-induced proliferation and apoptosis of human pulmonary artery smooth muscle cells via targeting TLR4

摘要

MicroRNAs (miRNAs) have a key role in the pathogenesis of pulmonary arterial hypertension (PAH), a disease characterized by enhanced proliferation and reduced apoptosis of pulmonary artery smooth muscle cells. In the present study, miR-760 was demonstrated to be downregulated in PAH lung tissues compared with normal lung tissues, an effect that may be associated with the development of PAH. Hypoxia is an important stimulus for human pulmonary artery smooth muscle cell (hPASMC) proliferation and the occurrence of PAH. Therefore, the effect of miR-760 in hypoxia-treated and normal hPASMCs was investigated. Expression of exogenous miR-760 decreased cell proliferation in hypoxia-induced hPASMCs, and promoted cell apoptosis with an increase in the BCL2 associated X/BCL2 ratio and the expression levels of Caspase-3 and Caspase-9. In addition, overexpression of miR-760 suppressed the migration of hPASMCs under hypoxic conditions. Furthermore, miR-760 was demonstrated to mediate its anti-proliferation effect via the regulation of toll-like receptor 4 (TLR4), a direct target of miR-760. The results revealed that knockdown of TLR4 restrained the hypoxia-induced hPASMC proliferation and induced cell apoptosis. The present study uncovered a novel regulatory pathway involving miR-760 and suggested that miR-760 may be explored as a potential therapy for PAH in the future.