PMID- 30186504 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 1792-0981 (Print) IS - 1792-1015 (Electronic) IS - 1792-0981 (Linking) VI - 16 IP - 3 DP - 2018 Sep TI - MicroRNA-126 accelerates IgE-mediated mast cell degranulation associated with the PI3K/Akt signaling pathway by promoting Ca(2+) influx. PG - 2763-2769 LID - 10.3892/etm.2018.6510 [doi] AB - 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 (Ca(2+)) 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 beta-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, Ca(2+) 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 Ca(2+) influx. This suggests that miR-126 may be a promising therapeutic target for the treatment of allergic skin diseases. FAU - Bao, Yuan AU - Bao Y AD - Department of Network Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China. FAU - Wang, Song AU - Wang S AD - Department of Massage, Wuhan Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430014, P.R. China. FAU - Gao, Yang AU - Gao Y AD - Department of Massage, Wuhan Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430014, P.R. China. FAU - Zhang, Wen AU - Zhang W AD - Department of Encephalopathy (I), Wuhan Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430014, P.R. China. FAU - Jin, Haitao AU - Jin H AD - Department of Encephalopathy (II), Wuhan Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430014, P.R. China. FAU - Yang, Yang AU - Yang Y AD - Department of Network Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China. FAU - Li, Jiangyu AU - Li J AD - Department of Gerontology, Wuhan Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430014, P.R. China. LA - eng PT - Journal Article DEP - 20180723 PL - Greece TA - Exp Ther Med JT - Experimental and therapeutic medicine JID - 101531947 PMC - PMC6122504 OTO - NOTNLM OT - Ca2+ influx OT - allergic skin diseases OT - mast cells OT - microRNA-126 OT - phosphoinositide 3-kinase/protein kinase B signaling pathway EDAT- 2018/09/07 06:00 MHDA- 2018/09/07 06:01 PMCR- 2018/07/23 CRDT- 2018/09/07 06:00 PHST- 2017/08/24 00:00 [received] PHST- 2018/06/15 00:00 [accepted] PHST- 2018/09/07 06:00 [entrez] PHST- 2018/09/07 06:00 [pubmed] PHST- 2018/09/07 06:01 [medline] PHST- 2018/07/23 00:00 [pmc-release] AID - ETM-0-0-6510 [pii] AID - 10.3892/etm.2018.6510 [doi] PST - ppublish SO - Exp Ther Med. 2018 Sep;16(3):2763-2769. doi: 10.3892/etm.2018.6510. Epub 2018 Jul 23.