mitochondria UPR in Idiopathic interstitial pneumonia

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08632
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Jikei University School of Medicine
• Principal Investigator: hara hiromichi 東京慈恵会医科大学, 医学部, 准教授 (70398791)
• Co-Investigator(Kenkyū-buntansha): 荒屋 潤 東京慈恵会医科大学, 医学部, 教授 (90468679)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: IPF / ミトコンドリアUPR

Outline of Final Research Achievements

Mitochondria play important roles in the maintenance of intracellular homeostasis by　responding to accumulation of damaged protein and mitochondrial damage. These adaptive responses are named ‘mitochondrial UPR’
SSBP-1, a key regulator of mitochondria UPR, translocates to nucleus and promotes transcription of chaperons. In this study, we demonstrated that SSBP-1 and sirtuin 3 (a downstream regulator of mitochondria UPR) were decreased in IPF lung. Suppression of mitochondrial UPR by knockdown of SSBP-1 in fibroblasts promoted myofibroblast differentiation. Decreased mitochondrial UPR in IPF may be associated with IPF pathogenesis.

Free Research Field

びまん性肺疾患

Academic Significance and Societal Importance of the Research Achievements

特発性肺線維症（idiopathic interstitial pneumonia:IPF）肺組織では、種々の刺激により傷害された蛋白の蓄積やミトコンドリア傷害に対する適応反応であるミトコンドリアUPR(Unfolded Protein Response)が低下していた。ミトコンドリアUPR低下は線維化を促進し、IPF病態に関連すると考えられた。ミトコンドリアUPRを促進することがIPFの治療の新たな選択肢となる可能性が示唆された