Rcn3 Suppression Was Responsible for Partial Relief of Emphysema as Shown by Specific Type II Alveolar Epithelial Cell Rcn3 CKO Mouse Model

作者：Qianyu Zhang, Tong Wang, Jiawei Jin, Xiaoqian Shi, Aiben Huang, Zhenru Ma, Jiujie Li, Shiyu Wang, Z. Runlin, Qiuhong Fang · 发表于：International Journal of COPD · 年份：2021 · DOI：10.2147/copd.s272711 · 被引用次数：6 · 研究领域：Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Neonatal Respiratory Health Research、Chronic Obstructive Pulmonary Disease (COPD) Research

BACKGROUND: Chronic obstructive pulmonary disease (COPD), characterized by irreversible airflow limitation, is a highly prevalent lung disease worldwide and imposes increasing disease burdens globally. Emphysema is one of the primary pathological features contributing to the irreversible decline of pulmonary function in COPD patients, but the pathogenetic mechanisms remain unclear. Reticulocalbin 3 (Rcn3) is an endoplasmic reticulum (ER) lumen protein localized in the secretory pathway of living cells. Rcn3 in type II alveolar epithelial cell (AECIIs) has been reported to play a critical role in regulating perinatal lung development and bleomycin-induced lung injury-repair processes. We hypothesized that Rcn3 deficiency is associated with the development of emphysema during COPD, which is associated with the dysfunction of injury-repair modulated by alveolar epithelial cells. MATERIALS AND METHODS: We examined Rcn3 expression in lung specimens from COPD patients and non-COPD control patients undergoing lung lobectomy or pneumonectomy. Two mouse models of emphysema were established by cigarette smoke (CS) exposure and intratracheal instillation of porcine pancreatic elastase (PPE). Rcn3 expression was detected in the lung tissues from these mice. Furthermore, conditional knockout (CKO) mice with Rcn3 deletion specific to AECIIs were used to explore the role of Rcn3 in PPE-induced emphysema progression. Rcn3 protein expression in lung tissues was evaluated by Western blot and i...