Sirtuin3 reduces acute lung inflammation and emphysematous aggravation in COPD exacerbation mouse model

Backgrounds: Ｃhronic obstructive pulmonary disease (COPD) is a pulmonary disease with permanent airflow obstruction and emphysema, and acute exacerbation of COPD is often induced by infection often resulting in a poor prognosis. Reactive oxygen species (ROS), producted in mitochondria, has been reported to accelerate the establishment of COPD. Sirtuin3(SIRT3) is the mitochondrial NAD(+)-dependent deacetylase, which regulates ROS formation and proinflammatory responses. It is also reported to be related with lifespan longevity. Aims: The aim of our study was to investigate the role of SIRT3 in COPD exacerbation mouse model generated by porcine pancreatic elastase(PPE) and lipopolysaccharide(LPS). Methods: PPE followed by LPS was administered intratracheally to wild-type (WT) or SIRT3 overexpressing transgenic(SIRT3 OE), SIRT3 knockout (SIRT3 KO) male mice. The next day (early phase) and 4weeks later (late phase) after LPS administration, BALF analysis and lung function test was conducted. Results: In early phase, the BALF cell count of SIRT3 OE mice was significantly increased compared to control WT mice, whereas that of SIRT3 KO mice was significantly decreased. In late phase, the lung compliance was increased in SIRT3 OE mice compared to WT mice, and decreased in SIRT3 KO mice. Conclusions: Our study showed that SIRT3 surpressed acute lung injury and emphysematous worsening in COPD model mice. SIRT3 would serve as a new therapeutic target to COPD and COPD exacerbation.