Mast Cell-mediated MicroRNA Functioning in Immune Regulation and Disease Pathophysiology

Overview

Journal Clin Exp Med

Date 2025 Jan 15

PMID 39812911

Authors

Qiuping Deng

Xiuju Yao

Siyun Fang

Yueshan Sun

Lei Liu

Chao Li

Guangquan Li

Yuanbiao Guo

Jinbo Liu

Affiliations

Soon will be listed here.

Abstract

Upon stimulation and activation, mast cells (MCs) release soluble mediators, including histamine, proteases, and cytokines. These mediators are often stored within cytoplasmic granules in MCs and may be released in a granulated form. The secretion of cytokines and chemokines occurs within hours following activation, with the potential to result in chronic inflammation. In addition to their role in allergic inflammation, MCs are components of the tumor microenvironment (TME). MicroRNAs (miRNAs) are small RNA molecules that do not encode proteins, but regulate post-transcriptional gene expression by binding to the 3' non-coding regions of mRNAs. This plays a crucial role in the function of MC, including the key processes of MC proliferation, maturation, apoptosis, and activation. It has been demonstrated that miRNAs are also present in extracellular vesicles (EVs) secreted by MCs. EVs derived from MCs mediate intercellular communication by carrying miRNAs, affecting various diseases including allergic diseases, intestinal disorders, neuroinflammation, and tumors. These findings provide important insights into the therapeutic mechanisms and targets of miRNAs in MCs that affect diseases. This review discusses the relevance of miRNA production by MCs in regulating their own activity and the effect of miRNAs putatively produced by other cells in the control of MC activity and their participation in selected pathologies.

References

Xia Y, Wei K, Hu L, Zhou C, Lu Z, Zhan G . Exosome-mediated transfer of miR-1260b promotes cell invasion through Wnt/β-catenin signaling pathway in lung adenocarcinoma. J Cell Physiol. 2020; 235(10):6843-6853. DOI: 10.1002/jcp.29578. View

Santos P, Coutinho-Camillo C, Soares F, Freitas V, Vilas-Boas D, Xavier F . MicroRNAs expression pattern related to mast cell activation and angiogenesis in paraffin-embedded salivary gland tumors. Pathol Res Pract. 2017; 213(12):1470-1476. DOI: 10.1016/j.prp.2017.10.012. View

Wilfred B, Wang W, Nelson P . Energizing miRNA research: a review of the role of miRNAs in lipid metabolism, with a prediction that miR-103/107 regulates human metabolic pathways. Mol Genet Metab. 2007; 91(3):209-17. PMC: 1978064. DOI: 10.1016/j.ymgme.2007.03.011. View

Pfeiffer A, Bandara G, Petersen J, Falduto G, Zimmerberg J, Metcalfe D . Activation of the receptor KIT induces the secretion of exosome-like small extracellular vesicles. J Extracell Biol. 2024; 3(1):e139. PMC: 11080788. DOI: 10.1002/jex2.139. View

Yamada Y, Kosaka K, Miyazawa T, Kurata-Miura K, Yoshida T . miR-142-3p enhances FcεRI-mediated degranulation in mast cells. Biochem Biophys Res Commun. 2013; 443(3):980-6. DOI: 10.1016/j.bbrc.2013.12.078. View

Peng S, Zhang S, Fan X, Zhu J, Liu C, Yue Y . Integrative analysis of negatively regulated miRNA-mRNA axes for esophageal squamous cell carcinoma. Cancer Biomark. 2023; 37(3):191-203. DOI: 10.3233/CBM-220309. View

Carter M, Metcalfe D, Komarow H . Mastocytosis. Immunol Allergy Clin North Am. 2013; 34(1):181-96. PMC: 3863935. DOI: 10.1016/j.iac.2013.09.001. View

Acikalin M, Oner U, Topcu I, Yasar B, Kiper H, Colak E . Tumour angiogenesis and mast cell density in the prognostic assessment of colorectal carcinomas. Dig Liver Dis. 2005; 37(3):162-9. DOI: 10.1016/j.dld.2004.09.028. View

Kwon Y, Kim Y, Eom S, Kim M, Park D, Kim H . MicroRNA-26a/-26b-COX-2-MIP-2 Loop Regulates Allergic Inflammation and Allergic Inflammation-promoted Enhanced Tumorigenic and Metastatic Potential of Cancer Cells. J Biol Chem. 2015; 290(22):14245-66. PMC: 4447993. DOI: 10.1074/jbc.M115.645580. View

10.

Djuranovic S, Nahvi A, Green R . A parsimonious model for gene regulation by miRNAs. Science. 2011; 331(6017):550-3. PMC: 3955125. DOI: 10.1126/science.1191138. View

10.

Segura-Villalobos D, Lamas M, Gonzalez-Espinosa C . Cyclic Hypoxia Induces Transcriptomic Changes in Mast Cells Leading to a Hyperresponsive Phenotype after FcεRI Cross-Linking. Cells. 2022; 11(14). PMC: 9319477. DOI: 10.3390/cells11142239. View

11.

Man M, Hatano Y, Lee S, Man M, Chang S, Feingold K . Characterization of a hapten-induced, murine model with multiple features of atopic dermatitis: structural, immunologic, and biochemical changes following single versus multiple oxazolone challenges. J Invest Dermatol. 2007; 128(1):79-86. PMC: 2671229. DOI: 10.1038/sj.jid.5701011. View

12.

Li W, Liu F, Wang J, Long M, Wang Z . MicroRNA-21-Mediated Inhibition of Mast Cell Degranulation Involved in the Protective Effect of Berberine on 2,4-Dinitrofluorobenzene-Induced Allergic Contact Dermatitis in Rats via p38 Pathway. Inflammation. 2017; 41(2):689-699. DOI: 10.1007/s10753-017-0723-1. View

13.

Hu L, Si L, Dai X, Dong H, Ma Z, Sun Z . Exosomal miR-409-3p secreted from activated mast cells promotes microglial migration, activation and neuroinflammation by targeting Nr4a2 to activate the NF-κB pathway. J Neuroinflammation. 2021; 18(1):68. PMC: 7945321. DOI: 10.1186/s12974-021-02110-5. View

14.

Lu T, Lim E, Wen T, Plassard A, Hogan S, Martin L . MiR-375 is downregulated in epithelial cells after IL-13 stimulation and regulates an IL-13-induced epithelial transcriptome. Mucosal Immunol. 2012; 5(4):388-96. PMC: 4154234. DOI: 10.1038/mi.2012.16. View

15.

Shihui M, Shirong Y, Jing L, Jingjing H, Tongqian W, Tian T . S100A4 reprofiles lipid metabolism in mast cells via RAGE and PPAR-γ signaling pathway. Int Immunopharmacol. 2024; 128:111555. DOI: 10.1016/j.intimp.2024.111555. View

16.

Specjalski K, Jassem E . MicroRNAs: Potential Biomarkers and Targets of Therapy in Allergic Diseases?. Arch Immunol Ther Exp (Warsz). 2019; 67(4):213-223. PMC: 6597590. DOI: 10.1007/s00005-019-00547-4. View

17.

Lu C, Huang X, Zhang X, Roensch K, Cao Q, Nakayama K . miR-221 and miR-155 regulate human dendritic cell development, apoptosis, and IL-12 production through targeting of p27kip1, KPC1, and SOCS-1. Blood. 2011; 117(16):4293-303. PMC: 3087479. DOI: 10.1182/blood-2010-12-322503. View

18.

Fu D, Zhao H, Huang Y, Li J, Feng H, Li A . Metformin regulates the effects of IR and IGF-1R methylation on mast cell activation and airway reactivity in diabetic rats with asthma through miR-152-3p/DNMT1 axis. Cell Biol Toxicol. 2022; 39(4):1851-1872. DOI: 10.1007/s10565-022-09787-1. View

19.

Hershko A, Suzuki R, Charles N, Alvarez-Errico D, Sargent J, Laurence A . Mast cell interleukin-2 production contributes to suppression of chronic allergic dermatitis. Immunity. 2011; 35(4):562-71. PMC: 3432919. DOI: 10.1016/j.immuni.2011.07.013. View