Involvement of secreted microRNA and carrier exosomes in organ injury after hemorrhagic shock

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K11426
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: Nippon Medical School
• Principal Investigator: MASUNO TOMOHIKO 日本医科大学, 医学部, 講師 (00318528)
• Co-Investigator(Kenkyū-buntansha): 塚本 剛志 日本医科大学, 大学院医学研究科, 研究生 (20626270) ; 横田 裕行 日本医科大学, 大学院医学研究科, 大学院教授 (60182698) ; 新井 正徳 日本医科大学, 医学部, 講師 (60267127)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 出血性ショック / 臓器障害 / 腸管リンパ液 / microRNA / exosome

Outline of Final Research Achievements

Gut ischemia following hemorrhagic shock elaborates inflammatory mediators into the mesenteric lymph which result in subsequent distant organ injury. However, it is not clear how the mediators are transported to distant organs while maintaining their bioactivity. This study focused on secreted microRNAs (miRNAs) and exosomes as carriers of miRNAs to determine that exosome encapsulated miRNAs produced in mesenteric lymph are involved in the development of distant organ injury. miRNAs were present in rat mesenteric lymph and were found in the exosomes, as expected, but were also detected in the non-vesicle-associated fraction, suggesting that miRNAs may have alternative way to be transported other than the exosome-associated forms. Rat intestine epithelial cell line ICE6-derived exosomes injected from the mesenteric lymphatics were significantly accumulated in the lung, indicating that the lung was the primary target for exosomes encapsulating miRNAs produced from the intestine.

Free Research Field

救急医学

Academic Significance and Societal Importance of the Research Achievements

出血性ショック後に生じる多臓器不全による死亡率は依然高いままであり、その発生機序は未だ解明されていない。本研究結果において、腸管からリンパ液中に産生されるmiRNAはエキソゾームに内包される形で主要標的器官である肺へと運ばれ、組織内に取り込まれることが明らかとなった。本研究結果は、出血性ショック後急性肺障害をはじめとする遠隔臓器障害発生の病態解明に新たな展開をもたらすと考えられる。