title: miR-142-3p enhances FcεRI-mediated degranulation in mast cells.
abstract: Mast cells are immune cells derived from hematopoietic progenitors. When they are activated by stimuli, they immediately release granule-associated mediators, leading to allergic inflammation. Several factors controlling mediator release have been identified; however, little is known whether microRNAs (miRNAs) are involved in this process. miRNAs are a small class of non-coding RNAs that negatively regulate gene expression. In this study, we investigated the relationship between miRNAs and degranulation in LAD2 cells, a human mast cell line. We demonstrated that silencing of Dicer, a key enzyme of miRNA biogenesis, attenuates degranulation, indicating that miRNAs are involved in mast cell degranulation. We furthermore discovered that the overexpression of miR-142-3p enhances FcεRI-mediated degranulation and that miR-142-3p rescues the reduction of degranulation by silencing Dicer. Similar effects were observed in bone marrow-derived mast cells obtained miR-142-3p-deficient mice. Our studies suggest that miR-142-3p is a potential therapeutic target in pathological conditions caused by mast cells, such as mastocytosis and allergies.
authors.affiliation: Biologics Research Laboratories, Kyowa Hakko Kirin Co., Ltd., 3-6-6, Asahi-machi, Machida-shi, Tokyo 194-8533, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Biologics Research Laboratories, Kyowa Hakko Kirin Co., Ltd., 3-6-6, Asahi-machi, Machida-shi, Tokyo 194-8533, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Kosaka
authors.affiliation: Biologics Research Laboratories, Kyowa Hakko Kirin Co., Ltd., 3-6-6, Asahi-machi, Machida-shi, Tokyo 194-8533, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Miyazawa
authors.affiliation: Biologics Research Laboratories, Kyowa Hakko Kirin Co., Ltd., 3-6-6, Asahi-machi, Machida-shi, Tokyo 194-8533, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Kurata-Miura
authors.affiliation: Biologics Research Laboratories, Kyowa Hakko Kirin Co., Ltd., 3-6-6, Asahi-machi, Machida-shi, Tokyo 194-8533, Japan. Electronic address: tetsuo.yoshida@kyowa-kirin.co.jp.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Yoshida
mesh_terms: D000818:Animals; D001483:Base Sequence; D015550:Cell Degranulation; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D020868:Gene Silencing; D006801:Humans; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D017455:Receptors, IgE / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics; D043244:Ribonuclease III / Q000378:metabolism; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
chemical_list: D003598:Cytoskeletal Proteins; C543355:FcepsilonRI alpha-chain, human; C579617:FcepsilonRIalpha protein, mouse; C555159:MIRN142 microRNA, human; D035683:MicroRNAs; C529102:Mirn142 microRNA, mouse; D017455:Receptors, IgE; D003189:p-Methoxy-N-methylphenethylamine; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases
keywords: Degranulation; Mast cell; miR-142-3p; microRNA