Investigation of new therapeutic strategies for ARDS and lung cancer focusing on the regulation of sympathetic overactivity

Research Project

Project/Area Number	18K15929
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 Miyazaki
Principal Investigator	Hironobu Tsubouchi 宮崎大学, 医学部, 助教 (60573988)
Project Period (FY)	2018-04-01 – 2021-03-31
Project Status	Completed (Fiscal Year 2020)
Budget Amount *help	¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000) Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords	グレリン / ARDS / 肺癌 / 交感神経 / 癌
Outline of Final Research Achievements	Sympathetic overactivity is associated with inflammation and cancer progression. In LPS-treated mice, excessive doses of ghrelin reduced lung inflammation. In LPS-treated mice, excessive ghrelin administration reduced lung inflammation. The anti-inflammatory effect was also observed in vagotomized mice. Furthermore, the expression levels of pro-inflammatory cytokine in lungs of ghrelin receptor-deficient mice (GHSR-KO) were lower than those of wild type mice. These results suggest that endogenous ghrelin and pharmacological doses of ghrelin have different effects on inflammatory signals. The deletion of endogenous ghrelin caused development of lung cancer after intraperitoneal administration of urethane. It is suggested that defective ghrelin signaling may affect lung cancer carcinogenesis.
Academic Significance and Societal Importance of the Research Achievements	本研究の結果から、内因性グレリンの有無が難治性呼吸器疾患の一つであるARDSの病態の悪化に関与することが明らかになった。ARDSは有効な治療が確立されていない呼吸器疾患の一つであり、本研究で得られた知見が新しい治療法につながることが期待される。