MiR-140-3p Ameliorates The Inflammatory Response of Airway Smooth Muscle Cells by Targeting HMGB1 to Regulate The JAK2/STAT3 Signaling Pathway

Objective:The growth and migration of airway smooth muscle cells (ASMCs) are dysregulated in asthma. MicroRNAs(miRNAs) are associated with the pathogenesis of many diseases including asthma. Instead, the function of miR1403p in ASMCs’ dysregulation in asthma remains inconclusive. This study aimed to explore the role and mechanism ofmiR1403p in ASMCs’ dysregulation. Materials and Methods:In this experimental study, ASMCs were stimulated with plateletderived growth factor (PDGF)BB to construct an asthma cell model in vitro. MiR1403p expression level in the plasma of 50 asthmatic patients and50 healthy volunteers was measured with quantitative realtime polymerase chain reaction (qRTPCR). Besides, theenzymelinked immunosorbent assay (ELISA) was applied to detect the contents of interleukin (IL) 1β, IL6, and tumornecrosis factorα (TNFα) in the cell culture supernatant of ASMCs. Additionally, CCK8 and transwell assays wereadopted to probe the multiplication and migration of ASMCs. In addition, the western blot was employed to examineHMGB1, JAK2, and STAT3 protein expressions in ASMCs after miR1403p and HMGB1 were selectively regulated. Results: miR1403p expression was declined in asthmatic patients’ plasma and ASMCs stimulated by PDGFBB.Upregulating miR1403p suppressed the viability and migration of the cells and alleviated the inflammatory responsewhile inhibiting miR1403p showed opposite effects. Additionally, HMGB1 was testified as the target of miR1403p.HMGB1 overexpression could reverse the impact of miR1403p upregulation on the inflammatory response of ASMCsstimulated by PDGFBB. MiR1403p could repress the activation of JAK2/STAT3 via suppressing HMGB1. Conclusion: In ASMCs, miR1403p can inhibit the JAK2/STAT3 signaling pathway by targeting HMGB1, thusameliorating airway inflammation and remodeling in the pathogenesis of asthma.