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Intranasal Administration of Lentiviral miR-135a Regulates Mast Cell and Allergen-Induced Inflammation by Targeting GATA-3.

ABSTRACT: Mast cell (MC) degranulation is the foundation of the acute phase of allergic rhinitis (AR). Previously, downregulation of GATA binding protein 3 (GATA-3) was shown to suppress MC activation in an AR mouse model. Binding of microRNA-135a (miR-135a) to GATA-3 was also observed, and overexpression of this miRNA decreased GATA-3 mRNA and protein expression. However, the effects of miR-135a on MCs during AR are currently unknown. In the present study, we utilized a lentiviral (LV) vector to intranasally administer miR-135a to ovalbumin (OVA)-sensitized AR mice. Following miR-135a treatment, the total serum IgE concentration observed during AR was significantly reduced. In the nasal mucosa, the expression of T-box expressed in T cells (T-bet) was higher, whereas that of GATA-3 was lower in the AR mice following miRNA treatment. Notably, during AR, the ratio of type 1 T-helper cells (Th1) to type 2 (Th2) cells in the spleen is unbalanced, favoring Th2. However, administering miR-135a to the AR mice appeared to balance this ratio by increasing and decreasing the percentage of Th1 and Th2 cells, respectively. MiR-135a also appeared to strongly suppress the infiltration of eosinophils and MCs into the nasal mucosa, and it was specifically localized in the MCs, suggesting that its influence is modulated through regulation of GATA-3 in these cells. Additional work identifying the full therapeutic potential of miR-135a in the treatment of AR and diseases involving allergen-induced inflammation is warranted.

SUBMITTER: Deng YQ

PROVIDER: S-EPMC4587974 | biostudies-literature |

REPOSITORIES: biostudies-literature

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miR-135a Regulates Atrial Fibrillation by Targeting Smad3.

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| S-EPMC6301828 | biostudies-literature

Mast cells are required for full expression of allergen/SEB-induced skin inflammation.

Project description:Atopic dermatitis (AD) is a chronic pruritic inflammatory skin disease. We recently described an animal model in which repeated epicutaneous applications of a house dust mite extract and Staphylococcal enterotoxin B induced eczematous skin lesions. In this study we showed that global gene expression patterns are very similar between human AD skin and allergen/staphylococcal enterotoxin B-induced mouse skin lesions, particularly in the expression of genes related to epidermal growth/differentiation, skin barrier, lipid/energy metabolism, immune response, or extracellular matrix. In this model, mast cells and T cells, but not B cells or eosinophils, were shown to be required for the full expression of dermatitis, as revealed by reduced skin inflammation and reduced serum IgE levels in mice lacking mast cells or T cells (TCRβ(-/-) or Rag1(-/-)). The clinical severity of dermatitis correlated with the numbers of mast cells, but not eosinophils. Consistent with the idea that T helper type 2 (Th2) cells play a predominant role in allergic diseases, the receptor for the Th2-promoting cytokine thymic stromal lymphopoietin and the high-affinity IgE receptor, FcɛRI, were required to attain maximal clinical scores. Therefore, this clinically relevant model provides mechanistic insights into the pathogenic mechanism of human AD.

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| S-EPMC10390340 | biostudies-literature

miR-135a suppresses migration of gastric cancer cells by targeting TRAF5-mediated NF-κB activation.

Project description:BackgroundAs crucial regulators and possible biomarkers for cancer development, miRNAs have attracted intensive attention during the last two decades. Among the known miRNAs, miR-135a has been indicated as a tumor suppressor in several cancer types, whereas its roles and mechanisms in gastric cancer (GC) remain largely unclear.Materials and methodsQuantitative PCR (qPCR) was conducted to detect the expression of miR-135a in paired GC tissues as well as cell lines. The prognostic value was evaluated by Kaplan-Meier survival analysis. Wound healing and transwell assays were performed to determine the roles of miR-135a in GC cell migration. Dual-luciferase reporter assay, qPCR, and Western blot analysis were used to validate the targeting of TRAF5 and subsequent NF-κB pathway by miR-135a. Rescue experiments were done to explain the involvement of TRAF5 in mediating the anti-migration effect of miR-135a in GC cells. Finally, the expression of TRAF5 was examined in paired GC tissues.ResultsmiR-135a was confirmed to be decreased in GC tissues and cell lines, and its lower expression predicted worse overall survival. Cellular experiments proved that miR-135a suppressed migration in GC cells. Through directly targeting TRAF5 and subsequently inhibiting NF-κB pathway, miR-135a might efficiently inhibit GC cell metastasis. Furthermore, we found that TRAF5 overexpression was negatively correlated with miR-135a expression in GC tissues.ConclusionOur study indicated that miR-135a serves a suppressing role in GC cell migration by targeting TRAF5 and the downstream NF-κB pathway.

| S-EPMC6362934 | biostudies-literature

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