Midkine Ameliorates the LPS-Induced Apoptosis of Airway Smooth Muscle Cells Through the Notch2 Pathway

Background: Airway smooth muscle cells (ASMCs) produce several cytokines during inflammation, causing changes in extracellular matrix components, leading to airway remodeling. Midkine (MK) promotes the chemotaxis of inflammatory cells and releases proinflammatory factors. Whether Notch and Midkine jointly affect the proliferation and apoptosis of ASMCs is unknown. This research aimed to study the role of MK in ASMCs using an LPS-induced acute lung injury model. Methods: : ASMCs were cultured in vitro and divided into five groups according to treatment: control, lipopolysaccharide (LPS), non-target siRNA, MK siRNA, and g-secretase inhibitor LY411575. Cell proliferation was assessed using the Cell Counting Kit-8 assay. Apoptosis was measured by flow cytometry. Changes in the levels of cytokines related to the MK/Notch2 signaling pathway were detected by Western blotting, qPCR, and immunofluorescence. Results: : LPS increased the mRNA and protein expression of MK and Notch2. MK silencing and LY411575 reduced this effect. LPS reduced the viability and increased the rate of apoptosis of ASMCs. This effect was attenuated by exogenous MK and enhanced by MK silencing and LY411575 treatment. Conclusions: : The MK/Notch2 signaling pathway plays a regulatory role in ASMC proliferation and apoptosis in airway inflammation.