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

作者：Bao, Yuan; Wang, Song; Gao, Yang; Zhang, Wen; Jin, Haitao; Yang, Yang^*; Li, Jiangyu^*

来源：Experimental and Therapeutic Medicine, 2018, 16(3): 2763-2769.

DOI：10.3892/etm.2018.6510

• microRNA-126
• mast cells
• phosphoinositide 3-kinase
• protein kinase B signaling pathway
• Ca2+ influx
• allergic skin diseases

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 -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.

• 出版日期2018-9
• 单位武汉市中医医院; 武汉市中心医院; 华中科技大学