FSTL1 aggravates Cigarette smoke-induced airway inflammation and airway remodeling by regulating autophagy

Abstract

Background Cigarette smoke (CS) is a major risk factor for COPD. Follistatin-like protein 1(FSTL1), a critical factor during embryogenesis particularly in respiratory lung development, is a novel mediator related to inflammation and tissue remodeling. We tried to investigate the role of FSTL1 in CS-induced autophagy dysregulaton, airway inflammation and remodeling. Methods Serum and lung specimens were obtained from COPD patients and controls. Adult female wild-type (WT) mice, FSTL1+/- mice and FSTL1flox/+ mice were exposed to room air or chronic CS. Additionally, 3-methyladenine (3-MA) ,an inhibitor of autophagy, were applied in CS exposed WT mice. The lung tissue and serum from patients and murine models were tested for FSTL1 and autophagy associated protein expression by ELISA, western blotting and immunohistochemical. Autophagosome were observed by Electron Microscope Technology(EMT). LTB4, IL-8 and TNF-α in bronchoalveolar lavage fluid of mice were examined by ELISA. Airway remodeling and lung function were also assessed. Results Both FSTL1 and autophagy biomarkers increased in COPD patients and CS exposed WT mice. Autophagy activation was upregulated in CS exposed mice accompanied by airway remodeling and airway inflammation. FSTL1+/- mice showed a lower level of CS-induced autophagy compared with control mice. FSTL1+/- mice can also resist CS-induced inflammatory response, airway remodeling and impaired lung function. CS exposed WT mice with 3-MA pretreatment have a similar manifestation with CS exposed FSTL1+/- mice. Conclusions FSTL1 promotes CS-induced COPD by modulating autophagy, therefore targeting FSTL1 and autophagy may shed light on treating cigarette smoke induced COPD.