mi<scp>RNA</scp>‐155 controls mast cell activation by regulating the <scp>PI</scp>3Kγ pathway and anaphylaxis in a mouse model

Biethahn, Katharina; Orinska, Zane; Vigorito, Elena; Goyeneche-Patino, Diego A; Mirghomizadeh, Farhad; Föger, Niko; Bulfone–Paus∥, Silvia

doi:10.1111/all.12407

Cited by 46 publications

(49 citation statements)

References 34 publications

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“…Additionally, an increasing number of studies have identified altered miRNA expression in diverse immune responses and immunologic disorders [25][26][27][28][29][30][31][32][33]. In contrast, the expression and function of specific miRNAs during the differentiation, proliferation and activation of mast cells has received little attention [34][35][36][37][38][39][40][41]. Mayoral et al [37] reported that miR-221-222 were detectably up-regulated in BMMC stimulated for 1 h or 24 h with PMA and ionomycin, and regulated cell cycle checkpoints in mast cells in response to acute stimulation, Only individual miRNAs have been implicated in mast cell degranulation and cytokine production because of their role in the post-transcriptional fine-tuning mechanisms of gene expression, which are associated with the FcεRI signaling pathway [35,36,38,42].…”

Section: Introductionmentioning

confidence: 99%

Altered MicroRNA Expression Profiles in Activated Mast Cells Following IgE-FcεRI Cross-Linking with Antigen

Teng¹,

Zhang²,

Yu³

et al. 2015

Cell Physiol Biochem

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Background/Aims: MicroRNAs (miRNAs) are critical regulators of immune responses and immunologic disorders. However, little is known about miRNA expression and function during mast cell differentiation, proliferation and activation. This study aimed to determine the miRNA expression profiles in mast cells stimulated by immunoglobulin E (IgE) and antigen and to analyze the potential functions of specific miRNAs. Methods: Bone marrow-derived mast cells (BMMCs) generated from differentiated mouse bone marrow cells were untreated (Unstimu) or stimulated with IgE-antigen complexes for 1 h or 6 h (Stimu). The miRNA profiles were evaluated by miRNA microarray. MiRNA target gene prediction and enrichment analyses were performed using bioinformatics. Results: Seven significantly up-regulated and 10 down-regulated miRNAs were identified in the 1 h Stimu group relative to the Unstimu group (fold change>2; P<0.05). Of 8 miRNAs randomly selected from the 17 identified, the expression levels of 6 were confirmed by quantitative real-time PCR (qRT-PCR). The potential target genes of several candidate miRNAs were enriched in FcεRI signaling, response to stimulus and cellular exocytosis. Conclusion: The expression of many miRNAs changes following IgE-FcεRI cross-linking in activated mast cells, and these miRNAs probably play key regulatory roles in core signaling pathways and biological behaviors. Evaluating the functions of these characteristic miRNAs will further our understanding of IgE-associated allergic disease pathogenesis and the development of therapeutic strategies.

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Section: Introductionmentioning

confidence: 99%

Altered MicroRNA Expression Profiles in Activated Mast Cells Following IgE-FcεRI Cross-Linking with Antigen

Teng¹,

Zhang²,

Yu³

et al. 2015

Cell Physiol Biochem

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“…PIK3R6 is a phosphoinositide 3-kinase (PI3K)γ subunit (32). PI3Ks are classified as class I, II or III based on substrate binding and sequence homology.…”

Section: Discussionmentioning

confidence: 99%

Genome-scale transcriptional analysis reveals key genes associated with the development of type II diabetes in mice

Zhang

Han

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Diabetes mellitus is one of the primary diseases that pose a threat to human health. The focus of the present study is type II diabetes (T2D), which is caused by obesity and is the most prevalent type of diabetes. However, genome-scale transcriptional analysis of diabetic liver in the development process of T2D is yet to be further elucidated. Microassays were performed on liver tissue samples from three-, six-and nine-week-old db/db mice with diabetes and db/m mice to investigate differentially expressed mRNA. Based on the results of genome-scale transcriptional analysis, five genes were screened in the present study: chromobox 8 (CBX8), de-etiolated homolog 1 and damage specific DNA binding protein 1 associated 1 (DDA1), Phosphoinositide-3-kinase regulatory subunit 6 (PIK3R6), WD repeat domain 41 (WDR41) and Glycine Amidinotransferase (GATM). At three weeks of age, no significant differences in levels or ratios of expression were observed. However, at six and nine weeks, expression of CBX8, DDA1, PIK3R6 and WDR41 was significantly upregulated (P<0.05) in the db/db model group compared with the control group, whereas GATM expression was significantly downregulated (P<0.05). These results suggest that T2D-related differential expression of genes becomes more marked with age, which was confirmed via reverse transcription-quantitative polymerase chain reaction. Genome-scale transcriptional analysis in diabetic mice provided a novel insight into the molecular. events associated with the role of mRNAs in T2D development, with specific emphasis upon CBX8, DDA1, PIK3R6, GATM and WDR41. The results of the present study may provide rationale for the investigation of the target genes of these mRNAs in future studies.

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“…Mast cell degranulation and cytokine production are inhibited by both miR-155 and miR-223 and correlate with selective alterations in PI3K-AKT pathway activity, though the direct mRNA targets remain to be identified [39,40]. Degranulation and adherence in response to FcεR ligation are enhanced by both miR-142-3p and miR-221.…”

Section: Mirnas Participate In Gene Network That Regulate Signaling mentioning

confidence: 99%

“…miR-155 −/− mice have reduce airway hypersensitivity and increased passive cutaneous anaphylaxis responses [39,47]. T cell-intrinsic expression of miR-155 promotes airway hyperresponsiveness (AHR) in asthma models, in part through the regulation of the direct target S1pr1 and recruitment of effector cells to the lung [47,48].…”

Section: Mirna In the Treatment Of Allergic Diseasementioning

confidence: 99%

MicroRNA regulation of allergic inflammation and asthma

Pua

Ansel

2015

Current Opinion in Immunology

101

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miRNA‐155 controls mast cell activation by regulating the PI3Kγ pathway and anaphylaxis in a mouse model

Abstract: Thus, we suggest that miR-155 plays a critical role in FcεRI-mediated MC responses by modulating components of the PI3Kγ pathway. This newly identified mechanism of miRNA-controlled MC activation may affect the initiation and maintenance of allergic disorders.

Cited by 46 publications

References 34 publications

Altered MicroRNA Expression Profiles in Activated Mast Cells Following IgE-FcεRI Cross-Linking with Antigen

Altered MicroRNA Expression Profiles in Activated Mast Cells Following IgE-FcεRI Cross-Linking with Antigen

Genome-scale transcriptional analysis reveals key genes associated with the development of type II diabetes in mice

MicroRNA regulation of allergic inflammation and asthma

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