Overexpression of miR-155-5p Inhibits the Proliferation and Migration of IL-13-Induced Human Bronchial Smooth Muscle Cells by Suppressing TGF-β-Activated Kinase 1/MAP3K7-Binding Protein 2

Abstract

PurposeMolecular mechanisms leading to asthma is still ill-defined. Though the function of microRNAs (miRNAs) in asthma was previously reported, the involvement of miR-155 in important features of this disease remains unknown. The present study was designed to uncover the probable involvement of miR-155-5p in the proliferation and migration of IL-13-induced human bronchial smooth muscle cells (BSMCs) and the intrinsic regulatory mechanism.MethodsThe effects of different concentrations of IL-13 on the proliferation and migration of BSMCs as well as the expression of miR-155-5p and its predicted target transforming growth factor (TGF)-β-activated kinase 1/MAP3K7-binding protein 2 (TAB2) were investigated. The effects of miR-155-5p on the proliferation and migration of interleukin (IL)-13-induced BSMCs was determined in vitro using BSMCs transfected with miR-155 mimic/inhibitor and induced by a high concentration of IL-13. The quantitative real-time polymerase chain reaction (qRTPCR) was employed for determining the expression of miR-155-5p and TAB2. Western blotting was applied to analyze the expression of TAB2 at the protein level. Cell proliferation and migration were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Transwell assays, respectively.ResultsThe proliferation and migration of BSMCs were dose-dependently increased with IL-13 treatment. Contrariwise, IL-13 dose-dependently inhibited the expression of miR-155-5p in BSMCs. Mechanistic studies showed that inhibition of miR-155-5p further promoted the stimulatory effects of IL-13, whereas overexpression of miR-155 significantly inhibited these effects. In silico studies and luciferase reporter assays indicated that TAB2 was a negatively regulated miR-155-5p target.ConclusionsThese results suggested that miR-155-5p-inhibit the IL-13-induced proliferation and migration of BSMCs by targeting TAB2 and that the IL-13/miR-155/TAB2 pathway could serve as a therapeutic target for pulmonary diseases, especially asthma.

Upregulation of LncRNA Malat1 Induced Proliferation and Migration of Airway Smooth Muscle Cells via miR-150-eIF4E/Akt Signaling

“…From multitudinous candidate miRNAs, we selected nine miRNAs for further analysis since these miRNAs had been previously reported to be able to regulate the phenotype of asthmatic ASMCs. For example, miR-20b inhibits PDGF-induced human fetal ASMC proliferation by targeting STAT3; miR-155 inhibits IL-13-induced human ASMC proliferation and migration by targeting TGF-β-activated kinase 1/MAP3K7-binding protein 2; and miR-150 and miR-135a, upregulated by Schisandrin, inhibits ASMC proliferation and migration in asthmatic rats (Kuhn et al, 2010; Bartel et al, 2018; Shi et al, 2018). Next, we performed a series of experiments and found that in these miRNAs, Malat1 only could directly target miR-150, and regulate miR-150 expression.…”

MicroRNA-125a-3p affects smooth muscle cell function in vascular stenosis

“…Based on previous studies, it is recognized that abnormal expression profiles of miRNAs are closely related to the development of arteriosclerosis [9,15], and VSMC proliferation and migration occur at every stage of arteriosclerosis [7,16]. Recently, many studies have shown that miRNAs play a critical role in the regulation and control of VSMC proliferation and migration [17][18][19]. Here, miR-125a-3p was observed to be significantly reduced in arteriosclerosis and restenotic arteries compared with that of the control group.…”

The geranyl acetophenone tHGA attenuates human bronchial smooth muscle proliferation via inhibition of AKT phosphorylation

“…Lower chambers containing media with 0.1% FBS were included to serve as negative controls. Following a 6 hour incubation period, non-migrated cells (upper chamber) were removed with a sterile cotton swab 67 . Media was removed from the lower chamber followed by addition of 500 µL of fresh media and 100 µl of MTS solution and incubated for 4 hours followed by measurement of absorbance at 490 nm through microplate reader (Molecular Devices, California, USA) 68 .…”