Rcn3 Suppression Was Responsible for Partial Relief of Emphysema as Shown by Specific Type II Alveolar Epithelial Cell Rcn3 CKO Mouse Model
Authors Zhang Q, Wang T, Jin J, Shi X, Huang A, Ma Z, Li J, Wang S, Ma RZ, Fang Q
Received 21 July 2020
Accepted for publication 11 December 2020
Published 26 January 2021 Volume 2021:16 Pages 147—158
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Richard Russell
Qianyu Zhang,1,* Tong Wang,1,* Jiawei Jin,1,2 Xiaoqian Shi,2 Aiben Huang,3 Zhenru Ma,1 Jiujie Li,4 Shiyu Wang,4 Runlin Z. Ma,4,5 Qiuhong Fang1
1Department of Respiratory and Critical Care Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, People’s Republic of China; 2The Clinical Research Center, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, People’s Republic of China; 3Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, People’s Republic of China; 4School of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, People’s Republic of China; 5State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Qiuhong Fang
Department of Respiratory and Critical Care Medicine, Beijing Chaoyang Hospital, Capital Medical University, No. 8 Gongren Tiyuchang South Road, Chaoyang District, Beijing 100020, People’s Republic of China
Tel +86 10-85231451
Fax +86 10-85231412
Runlin Z. Ma
Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, S2-316 Building #2, West Beichen Road, Chaoyang District, Beijing 100101, People’s Republic of China
Tel +86 10-64806599
Fax +86 10-64806598
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 immunohistochemistry. Rcn3 mRNA expression in lung tissues was detected by qPCR.
Results: Rcn3 expression was significantly increased in the lung specimens from COPD patients versus non-COPD patients and the level of Rcn3 increase was associated with the degree of emphysema. Rcn3 expression were also significantly up-regulated in both CS-induced and PPE-induced emphysematous mouse lungs. Moreover, the selective ablation of Rcn3 in AECIIs significantly alleviated severity of the mouse emphysema in response to intratracheal installation of PPE.
Conclusion: Our data, for the first time, indicated that suppression of Rcn3 expression in AECIIs has a beneficial effect on PPE-induced emphysema.
Keywords: COPD, emphysema, Rcn3, type II alveolar epithelial cell
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