MicroRNA-485-3p Promotes the Inflammatory Response and Extracellular Matrix Deposition by Activating Wnt/β-Catenin Signaling in Human Airway Smooth Muscle Cells

Abstract

The aim of this study was to study the effects of microRNA (miR)-485-3p on the inflammatory response and extracellular matrix deposition of human airway smooth muscle cells (HASMCs). The levels of miR-485-3p and WIF1 in peripheral blood of pediatric asthma (PA) patients and controls were examined by quantitative real-time polymerase chain reaction (qRT-PCR). miR-485-3p inhibitor and mimic, together with negative control (NC) inhibitor/ mimic, were transfected into HASMCs treated with tumor necrosis factor (TNF)-α. The levels of eotaxin, interleukin (IL)-8, and IL-6 were analyzed by enzyme-linked immunosorbent assay (ELISA). Cellular immunofluorescence analysis of fibronectin was also performed. The target genes of miR-485-3p were predicted and validated using TargetScan and dual-luciferase reporter gene assay. The protein levels of IL-6, eotaxin, IL-8, collagen III, collagen I, MMP-9, TIMP-1, MMP-2, axin, β-catenin, phosphorylated β-catenin, GSK3β, p-GSK3β, and WIF1 were tested by Western blot. The level of miR-485-3p was increased, whereas expression of WIF1 was low in PA patients. In TNF-α-induced HASMCs, miR-485-3p overexpression promoted the inflammatory response and the accumulation of extracellular matrix. WIF1 was a direct target of miR-485-3p. Silencing miR-485-3p inhibited activation of Wnt/β-catenin signaling. The reductions in the inflammatory response and ECM accumulation caused by silencing miR-485-3p were induced by blocking Wnt/β-catenin signaling. Thus, miRNA-485-3p targets WIF1 and activates Wnt/β-catenin signaling, facilitating activation of the inflammatory response and ECM accumulation in HASMCs.

miR‐485‐3p targets SIRT1 in vascular smooth muscle cells mediating the occurrence of aortic dissection

“…In atherosclerosis, miR‐485‐3p targets Olr1 to regulate vascular inflammation and lipid transport, thereby participating in the development of the disease 14 . In paediatric asthma, miR‐485‐3p can also promote inflammatory response and extracellular matrix deposition by activating the Wnt/β‐catenin signalling pathway in human airway smooth muscle cells 27 . To uncover the function of miR‐485‐3p in AD, we conducted extensive research.…”

“… 14 In paediatric asthma, miR‐485‐3p can also promote inflammatory response and extracellular matrix deposition by activating the Wnt/β‐catenin signalling pathway in human airway smooth muscle cells. 27 To uncover the function of miR‐485‐3p in AD, we conducted extensive research. At the cellular level, we found that overexpression of miR‐485‐3p in HAVSMCs led to heightened inflammation and increased apoptosis, while downregulation of miR‐485‐3p suppressed these processes.…”