Identification of untranslated RNAs and their target molecular species involved in airway hyperresponsiveness after lung transplantation.

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K08864
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: International University of Health and Welfare
• Principal Investigator: Hanazaki Motohiko 国際医療福祉大学, 医学部, 教授 (60379790)
• Co-Investigator(Kenkyū-buntansha): 千葉 義彦 星薬科大学, 薬学部, 教授 (00287848) ; 倉橋 清泰 国際医療福祉大学, 医学部, 主任教授 (50234539)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: 肺移植 / 肺 / 虚血再潅流傷害 / マイクロRNA / 麻酔薬 / 気道過敏性

Outline of Final Research Achievements

We used cultured human bronchial smooth muscle cells under hypoxic conditions as a system to mimic ischemic conditions at the cellular level, and performed a comprehensive analysis of gene expression changes, including untranslated RNAs (ncRNAs). The RNA-Seq analysis showed that the expression of miR-659 was significantly downregulated in the hypoxic (1%) group compared to the normoxic (21%) group, suggesting an interaction with RhoA mRNA. On the other hand, no expression changes were observed for RhoA mRNA itself, suggesting that, as in the asthma model, a decreased translational repression mechanism by microRNAs may be involved in airway hyperresponsiveness after ischemia. Other interesting gene expression changes were also detected, and future studies are expected.

Free Research Field

麻酔科学

Academic Significance and Societal Importance of the Research Achievements

研究の目的は肺移植術後に気道過敏性が亢進するメカニズムを解明することである。ラット肺虚血再潅流(IR)傷害モデルを用いてWestern blot法、リアルタイムRT-PCR法を行いmiR-133a-3pおよびそのターゲットであるRhoAタンパク質が気道過敏性亢進の機序であることを解明した。またこの機序は吸入麻酔薬セボフルランで抑制され、麻酔薬が肺移植術の気道過敏性亢進を抑制することを示唆した。DNAアレイによる網羅的解析により各種遺伝子の発現がダイナミックに変動しIR傷害がもたらされる可能性を示唆した。