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

Abstract

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. miR-142 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-β and miR-142 inhibitors + si-TGF-β. We verified that miR-142 targets TGF-β using a dual-luciferase reporter assay. The expression levels of miR-142, TGF-β, 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-β expression. In ASMCs, the expression of TGF-β, EGFR, Akt, phosphorylated-Akt (p-Akt), Bcl-2 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-β. 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-β expression via a mechanism involving the EGFR signaling pathway.

CD2 Regulates Pathogenesis of Asthma Induced by House Dust Mice Extract

“…Furthermore, increased expression of several miRNAs inhibit ASMC proliferation or AHR via different pathways. Specifically, miR-19b-3p, miR23b-3p and miR-142-3p inhibit TGFβ-dependent ASMC proliferation (28)(29)(30). MiR-150-3p and miR-708-5p inhibit ASMC proliferation by downregulating BCYRN1 (31) and CD38 (33), respectively, while miR-384-5p reduces ASMC autophagy (32).…”

“…Furthermore, most of these miRNAs with the exception of miR-23b-3p, were increased in WT HDME mice in comparison to their PBS controls ( Figure 7B). Strikingly, in comparison to allergen-treated WT mice, Cd2 −/− HDMEtreated mice had higher expression of miRNAs that regulate polymeric mucin expression (24) (Figure 7C), inflammation (25)(26)(27) (Figure 7D), airway smooth muscle proliferation and AHR (28)(29)(30)(31)(32)(33) (Figure 7E). Recently it has been shown that Let-7 family of miRNAs can directly bind to the 3 ′ UTR of IL-13 mRNA and degrade it (34).…”

Inhalation of nebulized Mycobacterium vaccae can protect against allergic bronchial asthma in mice by regulating the TGF-β/Smad signal transduction pathway

“…The airway inflammation is orchestrated through multiple cell types, inflammatory mediators, and cytokines and involves a considerable number of conduction channels and regulatory networks. The manifestation of asthma is also brought about by the concerted effects of numerous pathways and large regulatory networks, such as the transforming growth factor β (TGF-β)/Smad signaling pathway [2], STAT3/NF-κB signaling pathway [3], IL-37 signaling pathway [4], Notch1-GATA3 signaling pathway [5], and many others [6][7][8][9].…”

17β-Estradiol Promotes Apoptosis in Airway Smooth Muscle Cells Through CD38/SIRT1/p53 Pathway

“…Hypoxia is recognized as a critical contributor to pulmonary diseases including asthma, airway obstruction and pulmonary hypertension (1–3). Hypoxia stimulates airway inflammation and remodeling, and subsequently induces apoptosis in airway smooth muscle cells (ASMCs) during airway remodeling (4). There is emerging evidence for sex differences in the incidence and progression of lung diseases, and sex hormones play crucial roles in these pathological processes (5).…”