MicroRNA-142 Inhibits Proliferation and Promotes Apoptosis in Airway Smooth Muscle Cells During Airway Remodeling in Asthmatic Rats via the Inhibition of TGF-beta-Dependent EGFR Signaling Pathway

作者：Wang, Jing; Wang, Hu-Shan; Su, Zhen-Bo^*

来源：Cellular Physiology and Biochemistry, 2018, 47(4): 1682-1695.

DOI：10.1159/000490986

• MicroRNA-142
• Transforming growth factor-beta
• EGFR signaling pathway
• Asthma
• Airway remodeling
• Airway smooth muscle cells
• Proliferation
• Apoptosis

Background/Aims: Asthma is a heterogeneous disease characterized by chronic airway inflammation resulting from airway hyper-responsiveness to diverse stimuli. In this study, we investigated whether microRNA-142 (miR-142) expression affects proliferation and apoptosis in airway smooth muscle cells (ASMCs) during airway remodeling in asthmatic rats. Methods: Thirty six Wistar rats were randomly classified into a control group and an model group. miR142 mimics and inhibitors were constructed, and ASMCs were transfected using liposomes according to the following groups: blank, negative control (NC), miR-142 mimics, miR-142 inhibitors, si-TGF-beta and miR-142 inhibitors + si-TGF-beta. We verified that miR-142 targets TGF-beta using a dual-luciferase reporter assay. The expression levels of miR-142, TGF-beta, EGFR and apoptosis signaling pathway-related genes were determined using RT-qPCR and western blotting. Changes in cell proliferation, cell cycle progression and apoptosis were analyzed using MTT assays and flow cytometry. Results: Rats with asthma had higher expression levels of EGFR and Akt and lower miR-142 levels. miR-142 was negatively correlated with TGF-beta expression. In ASMCs, the expression of TGF-beta, EGFR, Akt, phosphorylated-Akt (p-Akt), Bcl2 and Bcl-xl and the rate of early apoptosis were decreased while expression of Bax and p21 and the proliferation rate were elevated with the upregulation of miR-142. The opposite results were observed with the downregulation of miR-142. Finally, the proliferative rate was decreased while the apoptosis rate was increased and expression levels of EGFR, Akt, p-Akt, Bcl-2 and Bcl-xl were reduced while Bax and p21 were elevated in the ASMCs transfected with miR-142 inhibitors and si-TGF-beta. Conclusion: The results of our study suggest that miR-142 inhibits proliferation and promotes apoptosis in ASMCs during airway remodeling in asthmatic rats by inhibiting TGF-beta expression via a mechanism involving the EGFR signaling pathway.

• 出版日期2018
• 单位吉林大学