Analysis of the enzyme producing reactive sulfur species in chronic obstructive pulmonary disease and development of novel antioxidant therapeutics

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16104
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Tohoku University
• Principal Investigator: Sano Hirohito 東北大学, 大学病院, 非常勤講師 (20895916)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: COPD / 閉塞性肺疾患 / 酸化ストレス / 活性硫黄分子種 / CARS2

Outline of Final Research Achievements

This study revealed that in the lungs of chronic obstructive pulmonary disease (COPD) patients, the expression of CARS2, the primary enzyme responsible for producing reactive sulfur species, is decreased. Furthermore, employing CARS2-deficient mice in an elastase-induced emphysema model, it was observed that lung inflammation and emphysema were exacerbated compared to wild-type mice. The administration of reactive sulfur species donors ameliorated these pathological conditions, suggesting that the reduction of reactive sulfur species due to CARS2 deficiency may contribute to the pathogenesis of COPD.

Free Research Field

呼吸器内科

Academic Significance and Societal Importance of the Research Achievements

本研究は、COPD患者の肺ではCARS2酵素の発現が低下し、活性イオウ分子種が減少していることを初めて明らかにした。さらに、動物実験でCARS2欠損が肺の炎症と気腫化を増悪させ、活性イオウ供与体の投与でこれを改善できることを示した。これらの知見は、COPDの新しい病態メカニズムを提示するものである。また、活性イオウ分子種を補う新規治療薬の開発につながる可能性がある。現在の対症療法に加え、COPDの進行を抑制する根本的治療法の実現が期待できる。