Derlin-1 protects alveolar epithelial cells against endoplasmic reticulum stress-induced apoptosis

This study explores the function of Derlin-1 expression in the lungs of cigarette smoke-exposed, chronic obstructive pulmonary disease (COPD) rats, and investigates whether Derlin-1 reduces the apoptosis of RLE-6TN cells induced by cigarette smoke extract (CSE) through the activation of an endoplasmic reticulum-associated degradation mechanism. A COPD rat model was generated by exposure to passive smoking. Hematoxylin and eosin staining was used to determine the pathologic changes in the lungs, and the expression and distribution of Derlin-1 in the lung tissue were measured using immunohistochemistry. The Derlin-1 gene was knocked down using small interfering RNA (siRNA) in the RLE-6TN alveolar epithelial cell line or over-expressed using lentiviral transfection. The cell apoptotic rate was measured using flow cytometry. Lung structure destruction and obstructive pulmonary ventilation function impairment were measured in the cigarette smoke-exposed COPD rats. The Derlin-1 mRNA and protein expressions were significantly up-regulated in the rats' lungs after two months of smoke exposure and moderately decreased after four months of smoke exposure. CSE treatment up-regulated the expression of Derlin-1 mRNA and protein in RLE-6TN cells. The knockdown of Derlin-1 decreased the IRE1 protein expression, increased the expressions of CHOP and the p-JNK protein, and increased the apoptotic rate in the RLE-6TN cells. The over-expression of Derlin-1 led to an increased expression of IRE1, decreased CHOP and p-JNK expressions, and a reduced apoptotic rate. The results show that cigarette smoke promotes alveolar epithelial cell apoptosis via an ERS mechanism, and Derlin-1 plays a key role in protecting alveolar epithelial cells from the apoptosis induced by cigarette smoke.