2022 Fiscal Year Final Research Report
The Role of Reactive Sulfur Species in Refractory Respiratory Diseases
| Project/Area Number |
20H03684
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 53030:Respiratory medicine-related
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 活性硫黄分氏種 / 酸化ストレス / 慢性閉塞性肺疾患 / 組織障害 / 間質性肺炎 |
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| Outline of Final Research Achievements |
This study elucidated the role of the reactive species (RSS) in refractory respiratory disease.
Mice heterozygous for the CARS2 gene, the enzyme responsible for the production of RSS, showed exacerbation of emphysema lesions by elastase or tobacco smoke extract. In vitro studies of lung constructs showed that RSS was important for suppressing inflammatory cytokine production, reducing oxidative stress, and inhibiting cellular senescence. COPD-derived lung constructs showed decreased expression of CARS2, which was associated with respiratory function. In a bleomycin-induced pulmonary fibrosis model, CARS2-deficient mice showed worsening of fibrotic lesions.
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| Free Research Field |
呼吸器内科学
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| Academic Significance and Societal Importance of the Research Achievements |
COPDをはじめとする難治性呼吸器疾患の病態は不明な点が多く、肺の抗酸化分子の観点からの研究は少ない。我々は肺における活性硫黄分子種(reactive sulfur species: RSS)の存在を明らかにした。RSSの産生酵素であるCARS2のヘテロ欠損マウスを作成し、このマウスを元にCOPDモデル及び肺線維症モデルマウスを作成し検討したところ野生型と比較して欠損マウスでは各疾患モデルの病態の悪化が認められた。さらにCOPD患者由来の肺組織、肺細胞ではCARS2の発現が低下し、肺の呼吸機能とも関連することを明らかにした。以上より難治性呼吸器疾患の病態改善に寄与する可能性が示唆された。
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