Targeting vascular endothelial mitochondrial Sirt3 for the treatment of post-ARDS pulmonary fibrosis

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K23980
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0903:Organ-based internal medicine and related fields
• Research Institution: University of Tsukuba
• Principal Investigator: Suzuki Toshio 筑波大学, 医学医療系, 講師 (70771856)
• Project Period (FY): 2019-08-30 – 2023-03-31
• Keywords: Sirt3 / 異常リモデリング / 肺血管内皮 / 内皮間葉転換 / ARDS / 肺線維症

Outline of Final Research Achievements

Expression of Sirt3 and its deacetylation targets, the antioxidant genes IDH2 and SOD2, was lower in fibrotic lungs than in healthy lungs. Investigation of human pulmonary vascular endothelial cells revealed that Sirt3-siRNA increased mitochondrial DNA damage and EndMT, and analysis using a mouse model of post-ARDS pulmonary fibrosis generated by repeated LPS administration showed that Sirt3-related EndMT was identified at the capillary level. The drug effect of Sirt3 activator, dihydromyricetin on post-ARDS pulmonary fibrosis pulmosphere model could not be confirmed.

Free Research Field

呼吸器内科学

Academic Significance and Societal Importance of the Research Achievements

本研究を開始して間もなく、新型コロナウイルスの世界的流行が始まり、post ARDS pulmonary fibrosisが「コロナ後遺症」として認知されるに至った。上皮細胞への傷害を起点に線維化が誘発されるのではなく、血管内皮を起点に誘発される病態形成は新型コロナウイルス感染症においてもあてはまり、その病態の一端を探索する形となった。