The role of fatty acid composition and Sestrin in progression of pulmonary emphysema.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09643
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Gunma University
• Principal Investigator: Yokoyama Tomoyuki 群馬大学, 大学院保健学研究科, 教授 (70312890)
• Co-Investigator(Kenkyū-buntansha): 前野 敏孝 群馬大学, 大学院医学系研究科, 准教授 (00436297) ; 須永 浩章 群馬大学, 大学院医学系研究科, 研究員 (10760077) ; 松井 弘樹 群馬大学, 大学院保健学研究科, 准教授 (20431710)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 遊離脂肪酸 / Elovl6 / 肺気腫 / Sestrin / α1アンチトリプシン

Outline of Final Research Achievements

We examined the role of Elongation of long chain fatty acid member 6 (Elovl6) which is a rate-limiting enzyme catalysing the elongation of saturated and monounsaturated fatty acids on the development of pulmonary emphysema using Elovl6-deficient mice. In the lung tissues of Elovl6-deficient mice, the expressions of Sestrin-1, -2 and -3 were reduced in Elovl6-deficient mice, and those reductions were more significant in mice exposed to tobacco. Meanwhile, as a result of comprehensive screening of gene expression by RNA sequence, we pay attention on SerpinA1.We found that the expression of SerpinA1 in the liver of Elovl6-deficient mice was significantly reduced, and the serum concentration of Elovl6-deficient mice was also decreased in comparison with those in control mice.

Free Research Field

循環器内科

Academic Significance and Societal Importance of the Research Achievements

肺胞上皮細胞の脂肪酸組成を制御するElongation of long chain fatty acid member 6 (Elovl6)の発現と肺気腫との関係をElovl6欠損マウスを用いて検討した。Elovl6欠損マウスではα1-アンチトリプシンの血中濃度低下に伴って先天性の肺気腫様病変を呈し、さらに、喫煙曝露によって、α1-アンチトリプシンの活性が低下して肺気腫病変が増悪した可能性がある。したがって、肝臓での脂肪酸バランス変化が血中のα1-アンチトリプシン活性を制御することで肺疾患の発症・進展に起因することが示唆され、肺気腫の新たな治療法の開発に繋がることが期待される。