Elucidation of the mechanism of cholesterol synthesis activation in pulmonary nontuberculous mycobacterial disease and its application to treatment

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15917
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: University of Tsukuba
• Principal Investigator: Matsuyama Masashi 筑波大学, 附属病院, 病院講師 (30816111)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: RNA-seq / 遺伝子発現解析 / Nrf2

Outline of Final Research Achievements

To investigate the effect of M. avium infection on the lung tissues of mice, comprehensive gene expression analysis by RNA-seq was performed on wild-type lung tissues 2 months after M. avium infection. In addition to the activity of TLR signals, the importance of Th1 /Th17 immunity, PD-1 pathway, and Nrf2 pathway was shown in this infected wild-type mice model by RNA-seq analysis.
Moreover, an experiment was conducted in which mice lacking the Nrf2 gene, which is a redox-sensitive transcription factor that regulates the expression of antioxidant and detoxification genes, were infected with M. avium. Then, this experiment discovered that Nrf2 protects against M. avium infection by regulating HO-1 and Nramp1.

Free Research Field

肺非結核性抗酸菌症

Academic Significance and Societal Importance of the Research Achievements

申請者は、M. avium感染2カ月後の野生型マウス肺組織で、RNA-seqによる網羅的な遺伝子発現解析を実施した。その結果、TLRシグナル、Th1/Th17免疫、PD-1経路、Nrf2経路などの重要な遺伝子発現経路が明らかになった。この情報は、今後の抗酸菌研究の重要なライブラリーになる可能性が高く、社会的意義は大きい。さらに、Nrf2がM. avium感染に重要であることが明らかになり、今後の新規治療方法を考慮するのに重要な報告となった。