MiR‐199‐3p–Dnmt3a–STAT3 signalling pathway in ovalbumin‐induced allergic rhinitis

Cui, Xinhua; Guo, Ying; Wang, Qirong; Li, Xuezhong

doi:10.1113/ep087751

Cited by 19 publications

(9 citation statements)

References 36 publications

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“…Overexpressed miR-199-3p enhanced cell proliferation and suppressed cell apoptosis in chondrocytes to attenuate knee osteoarthritis in mice 27 . miR-199-3p was found to be elevated in allergic rhinitis; the inhibition of miR-199-3p was proven to alleviate allergic rhinitis via Dnmt3a/STAT3 signal pathway in mouse 28 . In addition, miR-199-3p activated ERK1/2 pathway and IL-10 generation through targeting PARP-1 in systemic lupus erythematosus, indicating the anti-inflammatory effect of miR-199-3p 29 .…”

Section: Discussionmentioning

confidence: 99%

MiR-199-3p Suppressed Inflammatory Response by Targeting MECP2 to Alleviate RTX-Induced PHN in Mice

et al. 2022

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Varicella zoster virus–induced postherpetic neuralgia (PHN) can be alleviated by limited medications with serious side effects. This study aims to investigate the underlying molecular mechanism of miR-199-3p in mediating PHN in mice. 293T cells were transfected with miR-199-3p vectors (mimic/inhibitor). The target relationship between miR-199-3p and MECP2 was confirmed using luciferase reporter assay. PHN mouse model was established by TRX injection. Animal behaviors were evaluated using Hargreaves test and Von Frey test. Western blot was used for protein analysis, and quantitative reverse transcription polymerase chain reaction was performed for messenger RNA quantification. Serum levels of inflammatory mediators were determined using ELISA. Paw withdrawal latency (PWL) and mechanical withdrawal threshold (MWT) were decreased in resiniferatoxin-induced PHN mice. Downregulated miR-199-3p and upregulated MECP2 were found in PHN mice. Upregulated miR-199-3p increased PWL and MWT, but inhibited MECP2 in PHN mice. Besides, increased miR-199-3p suppressed proinflammatory indicators and activated anti-inflammatory mediators. It also found that MECP2 was the target of miR-199-3p. Further study showed miR-199-3p enhanced PWL and MWT, and supported inflammatory response via targeting MECP2. miR-199-3p regulated inflammation by targeting MECP2 to alleviate TRX-induced PHN in mice.

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Section: Discussionmentioning

confidence: 99%

MiR-199-3p Suppressed Inflammatory Response by Targeting MECP2 to Alleviate RTX-Induced PHN in Mice

et al. 2022

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“…A recent study showed that the levels of p-STAT3 and IL17 in nasal mucosa were elevated in AR patients. 43 Cui et al 44 reported that elevated expression of STAT3 led to the overexpression of IgE and other inflammatory factors in an OVA-induced AR model. However, Chiba et al 19 suggested that STAT3 phosphorylation could not be induced by antigens in the lungs of a mouse asthma model.…”

Section: Discussionmentioning

confidence: 99%

Activation of STAT6 by intranasal allergens correlated with the development of eosinophilic chronic rhinosinusitis in a mouse model

Wei

Sun

et al. 2022

Int J Immunopathol Pharmacol

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Eosinophilic chronic rhinosinusitis (ECRS) is a chronic inflammatory disease characterized by prominent eosinophilic infiltration along with a T-helper-2 (Th2) response. It has been well documented that signal transducer and activator of transcription 6 (STAT6) is a nuclear transcription factor that mediates Th2-type immunity and is implicatory of STAT1 and STAT3 in the pathogenesis of allergic airway diseases. However, little is known about the association between STATs and ECRS. Here, we explored the relationship between STAT1, STAT3, and/or STAT6 and eosinophilic inflammation accompanied by Th2-type immunity in a mouse model of ECRS. An ovalbumin (OVA)-staphylococcal enterotoxin B (SEB)-induced ECRS murine model was first established. The mucosal histological alterations were determined using hematoxylin and eosin staining. The number of eosinophils in peripheral blood was measured using a blood cell analyzer. The cytokine (IL-4, IL-5, IL17 A and IFN-γ) expression levels in the sinonasal mucosa and total and OVA-specific IgE from serum were measured using ELISA. Then, the protein levels of STAT1, STAT3, STAT6, phosphorylated STAT1 (p-STAT1), p-STAT3, p-STAT6, T-box expressed in T-cells (T-bet), GATA binding protein 3 (GATA-3), and retinoic acid receptor-related orphan receptor γ (RORγt) in the sinonasal mucosa were examined by immunohistochemical staining or Western blotting. Local administration of OVA combined with SEB (OVA + SEB) induced multiple polyp-like lesions, accompanied by prominent eosinophilic infiltration in the sinonasal mucosa. The OVA- and OVA+SEB-treated groups showed significantly higher eosinophil counts from peripheral blood and total and OVA-specific IgE levels from serum than those in the PBS- and SEB-treated groups. The levels of p-STAT6 were markedly increased by OVA + SEB exposure, as well as GATA-3, IL-4, and IL-5, but did not affect STAT6, p-STAT1, p-STAT3, T-bet, RORγt, IFN-γ, or IL-17A. Furthermore, an eosinophil count in the sinonasal mucosa showed a positive correlation with the level of p-STAT6 in the ECRS mouse model. Signal transducer and activator of transcription 6 signaling could be activated in the OVA+SEB-induced ECRS model and might be a crucial signal transducer in the development of Th2-skewed ECRS.

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“…19,21 For example, miR-199-3p targets Dnmt3a, resulting in hypermethylation of promoter as well as overexpression of signal transducer and activator of transcription 3(STAT3), ultimately leading to AR symptoms. 22 The anti-inflammatory effect of miR-146a on AR may act by inhibiting the toll-like receptor4 (TLR4)/TNF receptor-associated factor 6 (TRAF6)/nuclear factor kappa-B (NF-κB) signaling pathway. 23 Matrilin 2(MATN2) can be directly targeted by miR-202-5p, and can reverse miR-202-5p-mediated M2 phenotypic polarization in AR.…”

Section: Discussionmentioning

confidence: 99%

MiR-224 ameliorates inflammation and symptoms in mouse model of allergic rhinitis by targeting CDK9

Wang

et al. 2021

aei

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Objectives To explore the regulatory effects of microRNA (miRNA)-224 and its potential target gene, cyclin dependent kinase 9 (CDK9), in the pathological process of allergic rhinitis (AR). Methods To investigate the role of miR-224 and CDK9, it was screened by bioinformatics prediction software and verified by dual-luciferase reporter assay. The mouse model of AR was established by ovalbumin (OVA).The animal models were intervened with miR-224 agomir, negative control agomir, and saline respectively. The symptoms of sneezing and nasal rubbing were recorded. The expressions of miR224, CDK9, and cytokines in the nasal mucosa of different groups were analyzed by rt-PCR or western blotting. Enzyme-linked immunoassay (ELISA) was used to evaluate the levels of IgE and Histamine (HA) in the serum. The infiltration of inflammatory cells in the nasal mucosa was studied by immunohistochemistry. The expression and distribution of CDK9 in the nasal mucosa of mice were revealed by immunofluorescence. Results In the nasal mucosa of the animal models, the level of miR-224 was downregulated, while that of CDK9 was upregulated. The upregulation of miR-224 by miR-224 agomir reduced the frequencies of nasal rubbing and sneezing, the expression of CDK9, the levels of cytokines, and the concentrations of IgE and HA. Moreover, miR-224 appeared to attenuate the infiltration of inflammatory cells and hypersecretion of glands in the nasal mucosa. The expression of CDK9, which was distributed under the mucosa, especially in the submucosa interstitial tissue, was significantly reduced. Conclusion MiR-224 affected the pathogenesis of AR by targeting CDK9. It proves that miR-224 could be a novel potential therapeutic target for AR.

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MiR‐199‐3p–Dnmt3a–STAT3 signalling pathway in ovalbumin‐induced allergic rhinitis

Cited by 19 publications

References 36 publications

MiR-199-3p Suppressed Inflammatory Response by Targeting MECP2 to Alleviate RTX-Induced PHN in Mice

MiR-199-3p Suppressed Inflammatory Response by Targeting MECP2 to Alleviate RTX-Induced PHN in Mice

Activation of STAT6 by intranasal allergens correlated with the development of eosinophilic chronic rhinosinusitis in a mouse model

MiR-224 ameliorates inflammation and symptoms in mouse model of allergic rhinitis by targeting CDK9

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