Endoplasmic Reticulum Stress Induces HRD1 to Protect Alveolar Type II Epithelial Cells from Apoptosis Induced by Cigarette Smoke Extract

Abstract

Background/Aims: Cigarette smoking is a major risk factor of chronic obstructive pulmonary disease. This study aimed to examine the effects of cigarette smoke extract (CSE) on alveolar type II epithelial cells (AECII) and investigate the underlying mechanism. Methods: Primary AECII were isolated from rat lung tissues and exposed to CSE. Apoptosis was detected by flow cytometry. Protein expression was detected by Western blot analysis. Results: Primary rat AECII maintained morphological and physiological characteristic after 3 passages. CSE increased the expression of ER specific pro-apoptosis factors CHOP and caspase 12, and the phosphorylation of JNK in AECII. CSE activated ER stress signaling and increased the phosphorylation of PERK, eIF2α and IRE1. Furthermore, CSE induced the expression of Hrd1, a key factor of ER-associated degradation, in AECII. Knockdown of Hrd1 led to more than 2 fold increase of apoptosis, while overexpression of Hrd1 attenuated CSE induced apoptosis of AECII. Conclusions: Our results suggest that ER stress induces HRD1 to protect alveolar type II epithelial cells from apoptosis induced by CSE.