MicroRNA‑126 accelerates IgE‑mediated mast cell degranulation associated with the PI3K/Akt signaling pathway by promoting Ca2+ influx

Bao,Yuan; Wang,Song; Gao,Yang; Zhang,Wen; Jin,Haitao; Yang,Yang; Li,Jiangyu

doi:10.3892/etm.2018.6510

MicroRNA‑126 accelerates IgE‑mediated mast cell degranulation associated with the PI3K/Akt signaling pathway by promoting Ca2+ influx

Authors:
- Yuan Bao
- Song Wang
- Yang Gao
- Wen Zhang
- Haitao Jin
- Yang Yang
- Jiangyu Li
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Affiliations: Department of Network Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China, Department of Massage, Wuhan Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430014, P.R. China, Department of Encephalopathy (I), Wuhan Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430014, P.R. China, Department of Encephalopathy (II), Wuhan Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430014, P.R. China, Department of Gerontology, Wuhan Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430014, P.R. China
Published online on: July 23, 2018 https://doi.org/10.3892/etm.2018.6510
Pages: 2763-2769

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Abstract

Mast cells (MCs) have been reported to serve a crucial role in allergic diseases, including asthma, allergic rhinitis and anaphylaxis. A previous study revealed that microRNA‑126 (miR‑126) was associated with airway hyperresponsiveness induced by house dust mites, however the molecular mechanisms were unclear. The present study aimed to investigate the effect of miR‑126 on immunoglobulin E (IgE)‑regulated MC degranulation and explore its underlying mechanisms. miR‑126 expression was quantified using a rat model in vivo and in rat peritoneal mast cells (RPMCs) in vitro. Overexpression or downregulation of miR‑126 was established by transfection with miR‑126 mimics or miR‑126 inhibitors and MC degranulation was subsequently evaluated. The effect of miR‑126 on protein kinase B (Akt) and phosphorylated Akt protein expression was examined by western blot analysis. The phosphoinositide 3‑kinase (PI3K) inhibitor (LY294002) was used to determine the role of the PI3K/Akt signaling pathway. In addition, cytosolic calcium (Ca2+) levels were measured by a fura‑2 assay. The results demonstrated that miR‑126 expression was upregulated in the ear tissues of rats with allergic contact dermatitis and IgE‑activated MCs. The overexpression of miR‑126 in RPMCs was established following miR‑126 mimic transfection. The release of β‑hexosaminidase and histamine, markers of MC degranulation, were significantly increased in cells with miR‑126 overexpression. The phosphorylation of Akt was significantly increased following transfection with miR‑126 mimics in stimulated cells, however the signaling activation was abrogated by LY294002. In addition, Ca2+ influx was significantly promoted in stimulated RPMCs overexpressing miR‑126. These results indicate that miR‑126 accelerated IgE‑mediated MC degranulation associated with the PI3K/Akt signaling pathway by promoting Ca2+ influx. This suggests that miR‑126 may be a promising therapeutic target for the treatment of allergic skin diseases.

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