关键词: 哮喘, miR-338-3p, 气道炎性反应, Ras同源基因(Rho)

Abstract: Objective To investigate the effects of miR-338-3p on interleukin (IL) -13-induced human bronchial epithelial cell line (BEAS-2B) injury and airway inflammation in mice with ovalbumin (OVA) -induced asthma. Methods OVA was used to replicate an asthma model of mice, which were divided into control group, model group, miR-NC agomir and miR-338-3p agomir intervention groups. HE staining microscopy was employed to observe the pathological morphology of lung tissue, while TUNEL staining was used to assess cell apoptosis in lung tissue. ELISA was conducted to measure the levels of interleukin-1β (IL-1β) and tumor necrosis factor (TNF)-α in lung tissue. The BEAS-2B cells were subjected to IL-13-induced injury and divided into control group, IL-13group, IL-13+miR-NC group, and IL-13+miR-338-3p mimic group. Cell viability was assessed with MTT assay. Flow cytometry was employed to evaluate cell apoptosis. The level of IL-1β and TNF-α in cells was measured by ELISA. The targeting relationship between miR-338-3p and Ras homologous (Rho) was investigated using bioinformatics analysis, luciferase assay, Western blot, and functional repair assay. Results Compared to the model group, the miR-338-3p agamid intervention group exhibited a significant reduction in inflammatory cell infiltration and airway wall thickening in lung tissue, as well as decreased cell apoptosis and the level of IL-1β and TNF-α in lung tissue (P＜0.05). Compared to the control group, cell viability of BEAS-2B cells in the IL-13+miR-338-3p mimic group exhibited a significant increase (P＜0.05), while apoptosis and level of IL-1β and TNF-α within the cells demonstrated a notable decrease (P＜0.05). Rho was a target gene of miR-338-3p, and over-expression of Rho attenuated the effect of miR-338-3p mimic on IL-13-induced injury and inflammation in BEAS-2B cells. Conclusions Up-regulation of miR-338-3p can inhibit asthma-related airway inflammation and injury of lung epithelial cells with a potential mechanism targeting at Rho gene.

Key words: asthma, miR-338-3p, airway inflammation, Ras homologous(Rho)