ASIC1a promotes alveolar epithelial apoptosis and acute lung injury through repression of the LncRNA00178/miR-466b-3p/Gucy1b1 ceRNA network.

Abstract

OBJECTIVE: Our previous studies have shown that acid-sensitive ion channel 1a (ASIC1a) promotes lipopolysaccharide (LPS)-induced acute lung injury (ALI), but the exact mechanism is unclear. This study explores the potential mechanism by which ASIC1a promotes ALI and provides new ideas for the development of new drugs. METHODS: The rats were divided into the normal group, ALI group and LPS + PcTx-1 group. Full transcriptomic RNA was screened from rat lung tissue via high-throughput sequencing and bioinformatics analysis. LPS-stimulated rat RLE-6TN cells were used to construct an ALI model in vitro, and plasmid transfection changed the expression of ASIC1a, LncRNA00178, miR-466b-3p, and Gucy1b1 in the cells to detect the effect of apoptosis on RLE-6TN cells. Moreover, the relationships between LncRNA00178 and miR-466b-3p or between miR-466b-3p and Gucy1b1 were verified via dual-luciferase reporter gene analysis. RESULTS: RNA screening of lung tissues revealed that the expression of LncRNA00178 was downregulated in the ALI model group and that the expression of LncRNA00178 was increased after the administration of Pctx-1. An in-depth mechanism analysis revealed that LncRNA00178 can directly bind to miR-466b-3p, thereby affecting the degradation of miR-466b-3p on its target messenger RNA (mRNA) Gucy1b1. ASIC1a mediates the apoptosis of alveolar epithelial cells in ALI by influencing the expression of LncRNA00178. CONCLUSION: In the pathological state of acute lung injury, ASIC1a negatively regulates LncRNA00178 and targets it to bind to miR-466b-3p, thereby inhibiting the expression of Gucy1b1, promoting the apoptosis of RLE-6TN cells and promoting the disease process of acute lung injury.