Elevated expression of microRNA-378 in children with asthma aggravates airway remodeling by promoting the proliferation and apoptosis resistance of airway smooth muscle cells.

The present study determined the expression of microRNA (miR)-378 in the peripheral blood and lung tissues of children with asthma, and investigated its effect and mechanism of action on the biological functions of airway smooth muscle cells. A total of 23 asthmatic children and 15 healthy children were included in the study. Peripheral blood and tissues were obtained from asthmatic children. Healthy children provided peripheral blood. Quantitative real-time polymerase chain reaction was used to determine the expression of miR-378. Airway smooth muscle cells were isolated and cultured in vitro. The cells were transfected with miR-378 mimics or miR-378 inhibitor. Following transfection, proliferation of the cells was determined using the CCK-8 assay. In addition, flow cytometry was used to detect the cell cycles and apoptosis of smooth muscle cells. Western blotting was performed to determine the expression of extracellular matrix proteins in smooth muscle cells. Furthermore, bioinformatics was used to predict potential target genes of miR-378 and their downstream signaling pathways. Results indicated that the expression of miR-378 in peripheral blood and lung tissues from asthmatic children was increased compared with that in healthy children. Serum from asthmatic children promoted the proliferation of smooth muscle cells in vitro by affecting the cell cycle, and enhanced apoptotic resistance of smooth muscle cells. Notably, overexpression of miR-378 increased the proliferation of smooth muscle cells by affecting the cell cycle, and this upregulated apoptotic resistance of smooth muscle cells and enhanced the expression of extracellular matrix-related proteins in smooth muscle cells. However, downregulation of miR-378 expression reversed the promoting effect of serum from asthmatic children on the biological functions of smooth muscle cells. These findings suggested that miR-378 possibly affects the proliferation, apoptosis and motility of airway smooth muscle cells via downstream signaling pathways. To conclude, the present study demonstrated that miR-378 expression was elevated in the peripheral blood and lung tissues from children with asthma. Furthermore, miR-378 promoted the biological functions of extracellular matrix-related proteins of smooth muscle cells, and possibly exerts its effect via its target genes through downstream signaling pathways.

Pubmed ID: 30783418 RIS Download