Crosstalk of exosome between lung and bone marrow in lung fibrosis

Research Project

Project/Area Number	15K19432
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Respiratory organ internal medicine
Research Institution	Nippon Medical School
Principal Investigator	Minoru Inomata 日本医科大学, 大学院医学研究科, 研究生 (50465291)
Project Period (FY)	2015-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000) Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000) Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000) Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Keywords	micro RNA / micro RNA 16 / C57BL/6 / bleomycin / anti-fibrotic effect / miR-16 / TGF / alpha-SMA / collage type I / SPARC / エクソソーム / 肺線維症 / miR 16 / miRNA / ブレオマイシン / マウス / マウスモデル
Outline of Final Research Achievements	Bleomycin was infused with osmotic pumps into C57BL/6 mice. Exosomes were extracted from serum of mice using ExoQuick. They were then, subjected to microarray analyses of each microRNA level in the exosomes using the miRNA microarray platform. In BLM-treated group, exosomal miR-16 increased by up to 10.32-fold on day 14 when compared with that in saline-treated group. MiR-16 mimic administration on day 14 after BLM-challenge significantly ameliorated pulmonary fibrosis. HFL-1 cells were pretreated with miR-16 mimic for 24 h before the addition of TGF-beta1. Treatment with miR-16 mimic significantly inhibited fibrotic marker analyzed by qRT-PCR and western blotting.
Academic Significance and Societal Importance of the Research Achievements	肺線維化病態において、線維化病変由来のエクソソームには線維化を悪化させるmicro RNAが含まれていることが明らかとなり、特発性肺線維症の病態解明や新規治療薬の開発にもつながる可能性がある。