Possible involvement of epigenomic alterations in the development of bronchial smooth muscle hyperresponsiveness in allergic asthma

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08248
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Hoshi University
• Principal Investigator: Chiba Yoshihiko 星薬科大学, 薬学部, 教授 (00287848)
• Co-Investigator(Renkei-kenkyūsha): Sakai HIROYASU 星薬科大学, 薬学部, 准教授 (00328923)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: アレルギー性喘息 / 気道過敏性 / 気管支平滑筋 / RhoA / microRNA (miRNA) / long non-coding RNA / lncRNA

Outline of Final Research Achievements

The current study was performed to identify epigenetic changes associated with the pathogenesis of airway hyperresponsiveness (AHR) in asthma. In bronchial smooth muscles (BSMs) of mice with asthma, a BSM hyperresponsiveness with an up-regulation of RhoA protein was observed. The RhoA up-regulation induced by antigen tended to be augmented in BSMs of the F3 generation compared to those of the parents. A MeDIP-Seq analysis revealed 93 differentially methylated regions of CpG islands between the diseased and control BSMs. However, no change in the CpG methylation of RhoA gene was observed. Microarray analyses revealed 14 and 131 differentially expressed miRNAs and lncRNAs, respectively, in BSMs of the diseased mice. Some of the ncRNAs that might be associated with RhoA translation are also differentially expressed. These findings suggest that wide variety of epigenetic changes, including changes in functional ncRNA expression, in the BSMs are involved in the development of AHR in asthma.

Free Research Field

生理学、病態生理学、薬理学。特にアレルギー疾患時の平滑筋等の過敏性発症機序。