Loss of FCHSD1 leads to amelioration of chronic obstructive pulmonary disease

Significance Chronic obstructive pulmonary disease (COPD/emphysema) is a life-threatening disorder with high morbidity and mortality that is prevalent worldwide. It is characterized by destruction of the alveolar wall and a decline in lung function. However, few palliative therapies are currently available. We show that FCH and double SH3 domains 1 ( Fchsd1 ) knockout mice are protected against airspace enlargement induced by elastase. FCHSD1 deficiency enhanced nuclear translocation of NRF2 and attenuated elastase-induced reduction in SIRT1 levels, which reduced inflammation and apoptosis of lung cells. These data indicate that FCHSD1 promotes the initiation phase of emphysema development and indicate potential therapeutic targets for COPD.