TET2 stabilized by deubiquitinase USP21 ameliorates cigarette smoke-induced apoptosis in airway epithelial cells
Lijuan Luo,
Zihang Zeng,
Tiao Li,
Xiangming Liu,
Yanan Cui,
Yongguang Tao,
Yi Li,
Yan Chen
Affiliations
Lijuan Luo
Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Research Unit of Respiratory Disease, Central South University, Changsha, Hunan 410011, China; Diagnosis and Treatment center of Respiratory Disease, Central South University, Changsha, Hunan 410011, China; Clinical Medical Research Center for Pulmonary and Critical Care Medicine in Hunan Province, Changsha, Hunan 410011, China
Zihang Zeng
Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Research Unit of Respiratory Disease, Central South University, Changsha, Hunan 410011, China; Diagnosis and Treatment center of Respiratory Disease, Central South University, Changsha, Hunan 410011, China; Clinical Medical Research Center for Pulmonary and Critical Care Medicine in Hunan Province, Changsha, Hunan 410011, China
Tiao Li
Department of Pulmonary and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
Xiangming Liu
Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Research Unit of Respiratory Disease, Central South University, Changsha, Hunan 410011, China; Diagnosis and Treatment center of Respiratory Disease, Central South University, Changsha, Hunan 410011, China; Clinical Medical Research Center for Pulmonary and Critical Care Medicine in Hunan Province, Changsha, Hunan 410011, China
Yanan Cui
Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Research Unit of Respiratory Disease, Central South University, Changsha, Hunan 410011, China; Diagnosis and Treatment center of Respiratory Disease, Central South University, Changsha, Hunan 410011, China; Clinical Medical Research Center for Pulmonary and Critical Care Medicine in Hunan Province, Changsha, Hunan 410011, China
Yongguang Tao
Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China; NHC Key Laboratory of Carcinogenesis (Central South University), Cancer Research Institute and School of Basic Medicine, Central South University, Changsha, Hunan 410078, China
Yi Li
Department of Infectious Disease Department, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Corresponding author
Yan Chen
Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Research Unit of Respiratory Disease, Central South University, Changsha, Hunan 410011, China; Diagnosis and Treatment center of Respiratory Disease, Central South University, Changsha, Hunan 410011, China; Clinical Medical Research Center for Pulmonary and Critical Care Medicine in Hunan Province, Changsha, Hunan 410011, China; Corresponding author
Summary: DNA demethylase TET2 was related with lung function. However, the precise role of TET2 in cigarette smoke (CS)-induced apoptosis of airway epithelium cells, and the mechanisms involved, have yet to be elucidated. Here, we showed that CS decreased TET2 protein levels but had no significant effect on its mRNA levels in lung tissues of chronic obstructive pulmonary disease (COPD) patients and CS-induced COPD mice model and even in airway epithelial cell lines. TET2 could inhibit CS-induced apoptosis of airway epithelial cell in vivo and in vitro. Moreover, we identified ubiquitin-specific protease 21 (USP21) as a deubiquitinase of TET2 in airway epithelial cells. USP21 interacted with TET2 and inhibited CSE-induced TET2 degradation. USP21 downregulated decreased TET2 abundance and further reduced the anti-apoptosis effect of TET2. Thus, we draw a conclusion that the USP21/TET2 axis is involved in CS-induced apoptosis of airway epithelial cells.
