Egr-1 regulates autophagy in cigarette smoke-induced chronic obstructive pulmonary disease

Chen Z-H. et al. 2008. PLoS ONE 3(10):e3316.

Speaker: Peihua Wu (吳佩樺)                                           Time: 14:00-15:00, Apr 29, 2009

Commentator: Dr. Jiu-Yao Wang (王志堯 老師)            Place: Room 601

Abstract:

Chronic obstructive pulmonary disease (COPD) is the obstructive airway disease characterized by progressive and irreversible airflow limitation. COPD is caused by noxious particles or gases, most commonly from smoking, which triggers a chronic inflammation of the respiratory tract(Barnes, 2000). Recent studies have shown that apoptosis may contribute to lung cell death and tissue injury under cigarette smoke exposure. Autophagy is a dynamic process responsible for the degradation of cellular components or infectious agents through the lysosomal machinery(Kundu and Thompson, 2008). However, the possible role of autophagy in COPD currently remains unclear. In the current study, the authors found increased autophagy in lung tissues of COPD patients and cigarette smoke extract (CSE)-treated human pulmonary epithelial cells (HBE, SAE, and Beas-2B). Inhibition of microtubule-associated protein-1 light chain-3B (LC3B), a key component in autophagy, attennuated CSE-induced apoptosis. Comprehensive gene expression analysis identified the transcriptional regulator early growth response-1 (Egr-1) as the gene whose expression was significantly changed in COPD. Consistently, Egr-1 proteins were elevated by CSE in human pulmonary epthelial cells. CSE treatment increased E2F transcription factor 4 (E2F-4) and Egr-1 complex formation and their binding to LC3B promoter to regulate expression of LC3B. Finally, Egr-1 knockout mice displayed attenuated autophagy, apoptosis, and emphysema compared with wildtype mice under chronic cigarette smoke exposure. In conclusion, the authors declared the regulatory role of Egr-1 in autophagy and apoptosis under cigarette smoke exposure in vitro and in vivo.

References:

1.     Barnes, P.J. (2000). Chronic obstructive pulmonary disease. N Engl J Med 343, 269-280.

2.     Kundu, M., and Thompson, C.B. (2008). Autophagy: basic principles and relevance to disease. Annu Rev Pathol 3, 427-455.