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

Abstract

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 miR-140-3p in ASMCs’ dysregulation in asthma remains inconclusive. This study aimed to explore the role and mechanism ofmiR-140-3p in ASMCs’ dysregulation.Materials and Methods:In this experimental study, ASMCs were stimulated with platelet-derived growth factor (PDGF)-BB to construct an asthma cell model in vitro. MiR-140-3p expression level in the plasma of 50 asthmatic patients and50 healthy volunteers was measured with quantitative real-time polymerase chain reaction (qRT-PCR). Besides, theenzyme-linked immunosorbent assay (ELISA) was applied to detect the contents of interleukin (IL) -1β, IL-6, and tumornecrosis factor-α (TNF-α) in the cell culture supernatant of ASMCs. Additionally, CCK-8 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 miR-140-3p and HMGB1 were selectively regulated.Results:miR-140-3p expression was declined in asthmatic patients' plasma and ASMCs stimulated by PDGF-BB.Upregulating miR-140-3p suppressed the viability and migration of the cells and alleviated the inflammatory responsewhile inhibiting miR-140-3p showed opposite effects. Additionally, HMGB1 was testified as the target of miR-140-3p.HMGB1 overexpression could reverse the impact of miR-140-3p upregulation on the inflammatory response of ASMCsstimulated by PDGF-BB. MiR-140-3p could repress the activation of JAK2/STAT3 via suppressing HMGB1.Conclusion:In ASMCs, miR-140-3p can inhibit the JAK2/STAT3 signaling pathway by targeting HMGB1, thusameliorating airway inflammation and remodeling in the pathogenesis of asthma.

Keywords

• asthma
• hmgb1
• jak2/stat3
• mir-140-3p