MicroRNA-485 Modulates the TGF-β/ Smads Signaling Pathway in Chronic Asthmatic Mice by Targeting Smurf2

Abstract

Background/Aims: Chronic respiratory conditions continue to plague millions of people worldwide. We aimed to elucidate the detailed mechanisms of microRNA-485 (miR-485) in airway smooth muscle cell (ASMC) proliferation and apoptosis in chronic asthmatic mice. Methods: A mouse model of chronic asthma was established. Ovalbumin was used to induce chronic asthma in the mice. The levels of transforming growth factor β (TGF-β), interleukin (IL)-4, IL-5, IL-13 and IL-17 in bronchoalveolar lavage fluid in mice were measured by enzyme-linked immunoassays (ELISAs). ASMCs were transfected with miR-485 mimic, miR-485 inhibitor and siRNA-Smurf2. The reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analyses were applied to detect the mRNA and protein levels of Smurf2, α-SMA, TGF-β1 and decapentaplegic homolog (Smads). The MTT assay was utilized for cell proliferation, while flow cytometry was conducted to assess cell cycle distribution and apoptosis. Results: Lower expression of miR-485 and higher expression levels of TGF-β1, IL-4, IL-5, IL-13 and IL-17 were detected in mice with chronic asthma. Smurf2 was identified as the target gene of miR-485. Upregulation of miR-485 mimic and downregulation of Smurf2 decreased expression levels of Smurf2, α-SMA, TGF-β1 and Smad3, inhibited cell proliferation and increased apoptosis, while contrary results were observed in ASMCs transfected with miR-485 inhibitor. Conclusion: Overexpressed miR-485 inhibits cell proliferation and promotes apoptosis of ASMCs through the Smurf2-mediated TGF-β/Smads signaling pathway in mice with chronic asthma.

Role of MicroRNAs in Parkinson’s Disease

“…Some miR-485-mediated pathways suggested in the literature include apoptosis [95,96], immune modulation [97,98], iron homeostasis [99] and synaptic plasticity [100]. miR-485-5p can target matrix metalloprotease (MMP)-14 [97], a membrane protein that can promote axon regeneration when inhibited [101].…”

“…In contrast, conflicting observations were reported for miR-485 in regulating apoptosis. Wang et al (2018) demonstrated that miR-485 can target Smad ubiquitin regulatory factor 2 (Smurf2) and promote apoptosis through the Smurf2-mediated TGF-β/Smads signalling pathway in chronic asthmatic mouse models [95]. However, Chen and colleagues (2016) showed that miR-485-5p is able to target TNF receptor (TNFR)-associated death domain (TRADD) and prevent TNF-α-induced neuronal cell apoptosis [96].…”

Changes in circulating microRNA after recumbent isometric yoga practice by patients with myalgic encephalomyelitis/chronic fatigue syndrome: an explorative pilot study

“…miR-485 [58] as well as miR-19a [59] have inhibitory effects on TGF-β signaling and the expression levels of TGF-β1. Several studies, but not all [60], have reported that the blood level of TGF-β1 of patients with ME/CFS was higher than in healthy subjects [16].…”

MiR-203a-3p regulates TGF-β1-induced epithelial–mesenchymal transition (EMT) in asthma by regulating Smad3 pathway through SIX1

“…Although asthma is commonly diagnosed in childhood, it occurs in all age groups [3]. Ra et al reported that there was no significant difference between the prevalence rate of the elderly (>65) and that of the young people (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34) [4]. A lot of stimuli, including cold air and exercise, and other risk factors such as smoking, obesity and rhinitis contribute to asthma incidence [5][6][7].…”

“…In addition, miRNAs have been found to implicate in the regulation of TGF-β1/Smad pathway. For instance, miR-485 overexpression suppressed cell proliferation and induced apoptosis of airway smooth muscle cells (ASMCs) through the Smurf2-mediated TGF-β/Smads signaling pathway in mice with chronic asthma [22]. MiR-744 repressed bronchial epithelial cell proliferation by regulating Smad3 via targeting TGF-β1 in severe asthma [21].…”