Downregulation of miRNA-451a Promotes the Differentiation of CD4+ T Cells towards Th2 Cells by Upregulating ETS1 in Childhood Asthma

Wang, Tianyue; Zhou, Qianlan; Shang, Yunxiao

doi:10.1159/000509714

Cited by 22 publications

(13 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…miRNA play a crucial role in a variety of biological processes. In the past years, a great number of studies have also shown that miRNA plays a crucial influence in airway inflammation and airway smooth muscle cell proliferation in asthma ( 9 , 10 ). Our previous studies found that miR-23b inhibited the cell proliferation of airway smooth muscle cells ( 11 ).…”

Section: Introductionmentioning

confidence: 99%

Promotor Hypomethylation Mediated Upregulation of miR-23b-3p Targets PTEN to Promote Bronchial Epithelial-Mesenchymal Transition in Chronic Asthma

et al. 2022

View full text Add to dashboard Cite

Chronic asthma is characterized by airway inflammation and irreversible airway remodeling. Epithelial-mesenchymal transition (EMT) is a typical pathological change of airway remodeling. Our previous research demonstrated miR-23b inhibited airway smooth muscle proliferation while the function of miR-23b-3p has not been reported yet. Besides, miRNA is regulated by many factors, including DNA methylation. The function of miR-23b-3p and whether it is regulated by DNA methylation are worth exploring. Balb/c mice were given OVA sensitization to develop the asthmatic model. Expression of miR-23b-3p and EMT markers were measured by RT-qPCR, WB and immunohistochemistry (IHC). DNA methylation was detected by methylation-specific PCR (MSP) and the MassARRAY System. Asthmatic mice and TGF-β1-stimulated bronchial epithelial cells (BEAS-2B) showed EMT with increased miR-23b-3p. Overexpression of miR-23b-3p promoted EMT and migration, while inhibition of miR-23b-3p reversed these transitions. DNA methyltransferases were decreased in asthmatic mice. MSP and MassARRAY System detected the promotor of miR-23b showed DNA hypomethylation. DNA methyltransferase inhibitor 5’-AZA-CdZ increased the expression of miR-23b-3p. Meanwhile, PTEN was identified as a target gene of miR-23b-3p. Our results indicated that promotor hypomethylation mediated upregulation of miR-23b-3p targets PTEN to promote EMT in chronic asthma. miR-23b-3p and DNA methylation might be potential therapeutic targets for irreversible airway remodeling.

show abstract

Section: Introductionmentioning

confidence: 99%

Promotor Hypomethylation Mediated Upregulation of miR-23b-3p Targets PTEN to Promote Bronchial Epithelial-Mesenchymal Transition in Chronic Asthma

et al. 2022

View full text Add to dashboard Cite

show abstract

“…In childhood asthma, miRNA-451a was found to inhibit Th2 cell differentiation by down-regulating protooncogene 1 (ETS1). This study reveals that miRNA-451a-ETS1 axis dysfunction is a novel molecular mechanism that underlies the pathogenesis of childhood asthma [40]. A study has shown that miR-1165-3p targets IL-13 and PPM1A to control Th2 differentiation and pulmonary inflammation in asthma.…”

Section: Mirnas Regulation Of Th2 Differentiation Via Signaling Pathwaysmentioning

confidence: 84%

Epigenetic Regulation of Th2 Response in Asthma by Non-Coding RNAs

Niu¹,

Wang²,

Dong³

et al. 2022

Recent Advances in Asthma Research and Treatments

View full text Add to dashboard Cite

Asthma is a common chronic inflammatory disease. Pathogenic mechanism underlying asthma is complex. The inflammatory response of asthma includes lymphocytes (T, B cells), ILC2, eosinophils and other types of immune and inflammatory cells. T CD4+ T helper 2 cells (Th2 cells) are thought to play a central role in regulating the phenotype of allergic asthma. Asthma is often closely associated with Th1/Th2 cell imbalance. Non-coding RNAs (ncRNAs) are non-protein coding RNA molecules in the transcriptome, mainly including microRNAs (miRNAs), long non-coding RNAs and circRNAs, etc., which are widely found in eukaryotic transcriptome and participate in the regulation of a variety of biological processes. ncRNAs are considered to function as modulators of the immune system. Their biological changes represent an important mechanism for the development of immune-mediated diseases. This chapter mainly discusses the epigenetic regulation of Th2 cells and their cytokines in asthma by non-coding RNAs. It helps us to better understand the pathogenesis of asthma and find potential asthma biomarkers.

show abstract

“…The inflammatory mediators in asthma have been extensively studied for their roles in cell recruitment and cell activation [ 20 , 21 , 58 ]. We also quantified a number of cytokines in the BAL from the mice and found that WT OVA mice had significantly higher concentrations of IL-4, IL-5, IL-6, IL-13, and CXCL1 compared to the Lsp1 −/− mice.…”

Section: Discussionmentioning

confidence: 99%

“…The lack of effective treatment for the 5–10% of cases that comprise severe asthma account for bulk of the asthma-related healthcare costs [ 19 ]. Inflammatory mediators such as IL-4, IL-13 and CXCL1 have important regulatory roles in asthmatic cell recruitment and activation [ 20 , 21 ]. It appears that excessive migration of neutrophils and eosinophils may underlie the inflammation-associated structural and physiologic changes in the asthmatic lung.…”

Section: Introductionmentioning

confidence: 99%

Deficiency of leukocyte-specific protein 1 (LSP1) alleviates asthmatic inflammation in a mouse model

Nascimento

Schneberger

et al. 2022

Respir Res

View full text Add to dashboard Cite

Background Asthma is a major cause of morbidity and mortality in humans. The mechanisms of asthma are still not fully understood. Leukocyte-specific protein-1 (LSP-1) regulates neutrophil migration during acute lung inflammation. However, its role in asthma remains unknown. Methods An OVA-induced mouse asthma model in LSP1-deficient (Lsp1−/−) and wild-type (WT) 129/SvJ mice were used to test the hypothesis that the absence of LSP1 would inhibit airway hyperresponsiveness and lung inflammation. Results Light and electron microscopic immunocytochemistry and Western blotting showed that, compared with normal healthy lungs, the levels of LSP1 were increased in lungs of OVA-asthmatic mice. Compared to Lsp1−/− OVA mice, WT OVA mice had higher levels of leukocytes in broncho-alveolar lavage fluid and in the lung tissues (P < 0.05). The levels of OVA-specific IgE but not IgA and IgG1 in the serum of WT OVA mice was higher than that of Lsp1−/− OVA mice (P < 0.05). Deficiency of LSP1 significantly reduced the levels of IL-4, IL-5, IL-6, IL-13, and CXCL1 (P < 0.05) but not total proteins in broncho-alveolar lavage fluid in asthmatic mice. The airway hyper-responsiveness to methacholine in Lsp1−/− OVA mice was improved compared to WT OVA mice (P < 0.05). Histology revealed more inflammation (inflammatory cells, and airway and blood vessel wall thickening) in the lungs of WT OVA mice than in those of Lsp1−/− OVA mice. Finally, immunohistology showed localization of LSP1 protein in normal and asthmatic human lungs especially associated with the vascular endothelium and neutrophils. Conclusion These data show that LSP1 deficiency reduces airway hyper-responsiveness and lung inflammation, including leukocyte recruitment and cytokine expression, in a mouse model of asthma.

show abstract

Downregulation of miRNA-451a Promotes the Differentiation of CD4+ T Cells towards Th2 Cells by Upregulating ETS1 in Childhood Asthma

Cited by 22 publications

References 28 publications

Promotor Hypomethylation Mediated Upregulation of miR-23b-3p Targets PTEN to Promote Bronchial Epithelial-Mesenchymal Transition in Chronic Asthma

Promotor Hypomethylation Mediated Upregulation of miR-23b-3p Targets PTEN to Promote Bronchial Epithelial-Mesenchymal Transition in Chronic Asthma

Epigenetic Regulation of Th2 Response in Asthma by Non-Coding RNAs

Deficiency of leukocyte-specific protein 1 (LSP1) alleviates asthmatic inflammation in a mouse model

Contact Info

Product

Resources

About