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Analysis of lysophospholipids in acute lung injury and effect of gene delivery of lysophospholipid acyltransferase

Research Project

Project/Area Number 15K09234
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionKanazawa Medical University

Principal Investigator

OSANAI Kazuhiro  金沢医科大学, 医学部, 教授 (70221158)

Co-Investigator(Kenkyū-buntansha) 小林 誠  金沢医科大学, 医学部, 助教 (20460355)
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords急性肺傷害 / リゾリン脂質アシル其転移酵素 / アデノ随伴ウイルスベクター / 遺伝子導入 / リポポリサッカライド / リゾフォスファチジルコリンアシル基転移酵素1 / アデノ随伴ウイルス / リゾリン脂質 / リゾリン脂質アシル基転移酵素 / 肺胞Ⅱ型上皮細胞 / 急性呼吸窮迫症候群
Outline of Final Research Achievements

Acute respiratory distress syndrome (ARDS) is less treatable and highly lethal respiratory disease. The pathophysiology is acute lung injury, in which various proinflammatory lyso-phospholipids are generated from inflammatory cells. The purpose of this study is to clarify role of lyso-phospholipids in ARDS using less antigenic adeno-associated virus (AAV) vector. We have newly made a AAV6.2 serotype which presumably has higher affinity for lung cells and carried out gene delivery of lyso-phospholipid acyltransferase in vitro cell and in vivo animal experiments. We showed that the treatment improve A549 cell injury induced by lipopolysaccharide, and that the AAV vector can deliver the gene of interest into rat lungs.

Academic Significance and Societal Importance of the Research Achievements

急性呼吸窮迫症候群(ARDS)は治療法の少ない、死亡率の高い呼吸器疾患である。本研究は生体への抗原性の乏しく遺伝子導入に優れているとされるアデノ随伴ウイルス(AAV)ベクターを用いて、ARDSにおけるリゾリン脂質の役割を明らかにするとともに、ARDSに新たな治療法の可能性を提供することを目的とした。今回我々は肺細胞への親和性の高いとされる血清型AAV6.2を新たに作成し、リゾリン脂質アシル其転移酵素遺伝子導入を細胞レベル、動物個体レベルで行った。その結果、ARDS細胞モデルで改善が得られること、およびラット肺への遺伝子導入も可能であることが判明した。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (2 results)

All 2017

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Exogenous gene transfer of Rab38 small GTPase ameliorates aberrant lung surfactant homeostasis in Ruby rats2017

    • Author(s)
      Kazuhiro Osanai , Keisuke Nakase, Takashi Sakuma, Kazuaki Nishiki, Masafumi Nojiri, Ryo Kato, Masatoshi Saito, Yuki Fujimoto, Shiro Mizuno and Hirohisa Toga
    • Journal Title

      Respiratory Research

      Volume: 18 Issue: 1 Pages: 70-70

    • DOI

      10.1186/s12931-017-0549-2

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Exogenous expression of lysophosphatidylcholine acytransferase 1 attenuates oleic acid-induced acute lung injury in rats2017

    • Author(s)
      Kazuhiro Osanai
    • Organizer
      2017FASEB SRC(New Orleans, USA)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2020-03-30  

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