PMID- 31060565
OWN - NLM
STAT- MEDLINE
DCOM- 20191224
LR  - 20230714
IS  - 1465-993X (Electronic)
IS  - 1465-9921 (Print)
IS  - 1465-9921 (Linking)
VI  - 20
IP  - 1
DP  - 2019 May 6
TI  - The cullin4A is up-regulated in chronic obstructive pulmonary disease patient and 
      contributes to epithelial-mesenchymal transition in small airway epithelium.
PG  - 84
LID - 10.1186/s12931-019-1048-4 [doi]
LID - 84
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common respiratory 
      disease with high morbidity and mortality. The most important pathophysiological 
      change of COPD is airway obstruction. Airway obstruction can cause airflow 
      restriction and obstructive ventilation dysfunction. Currently, many studies have 
      shown that there is EMT phenomenon in the process of airway remodeling of COPD. 
      Cullin4A (CUL4A) is an E3 ubiquitin ligase that interacts with other factors to 
      form the E3 complex. Studies have shown that CLU4A is associated with EMT in 
      non-small cell lung cancer and other cancers. However, its relationship with EMT 
      in COPD has not been reported systematically. In this study, we detected the 
      expression of CUL4A in lung epithelium of COPD patients. In addition, the 
      regulatory effect and mechanism of CUL4A on EMT in COPD were clarified in small 
      airway epithelial cells. METHODS: The expression of CUL4A was assessed by 
      immunohistochemistry in lung epithelium specimens from smokers, non-smokers and 
      patients with chronic obstructive pulmonary disease. The role of CUL4A on 
      cigarette smoke extract (CSE)-induced epithelial-mesenchymal transition (EMT) in 
      human small airway epithelial cells (HSAEpiCs) was assessed by silencing or 
      overexpression CUL4A in vitro. Cigarette smoke is recognized as a high-risk 
      factor in the induction of COPD, and its damage to the airway involves airway 
      damage, airway inflammation and airway remodeling. RESULTS: The results shown 
      that CUL4A expression in small airway epithelium was significantly increased in 
      patients with COPD. We also observed a significant negative association between 
      CUL4A and FEV(1)%, a useful clinical marker for the diagnosis and evaluation of 
      COPD severity, in small airway epithelial cells. In vitro, CSE-induced EMT is 
      associated with high expression of CUL4A, and targeted silencing of CUL4A with 
      shRNA inhibits CSE-induced EMT in human small airway epithelial cells. 
      CONCLUSIONS: Our results showed that CUL4A was overexpressed in lung epithelium 
      of COPD patients, and CUL4A could regulate EMT of human small airway epithelium, 
      which revealed a new mechanism of remodeling of small airway epithelium of COPD 
      patients.
FAU - Ren, Yidan
AU  - Ren Y
AD  - Department of Anesthesiology, Qilu Hospital, Shandong University, Jinan, China.
AD  - Department of Clinical Laboratory, The Second Hospital of Shandong University, 
      Jinan, China.
AD  - International Biotechnology R&D Center, Shandong University School of Ocean, 
      Weihai, China.
FAU - Zhang, Yi
AU  - Zhang Y
AD  - Department of Respiratory Medicine, Qilu Hospital, Shandong University, Jinan, 
      China.
FAU - Fan, Lixia
AU  - Fan L
AD  - Department of Anesthesiology, Qilu Hospital, Shandong University, Jinan, China.
FAU - Jiao, Qinlian
AU  - Jiao Q
AD  - Department of Clinical Laboratory, The Second Hospital of Shandong University, 
      Jinan, China.
AD  - International Biotechnology R&D Center, Shandong University School of Ocean, 
      Weihai, China.
FAU - Wang, Yunshan
AU  - Wang Y
AD  - Department of Clinical Laboratory, The Second Hospital of Shandong University, 
      Jinan, China. wangyunshan135@126.com.
FAU - Wang, Qin
AU  - Wang Q
AUID- ORCID: 0000-0001-7759-0238
AD  - Department of Anesthesiology, Qilu Hospital, Shandong University, Jinan, China. 
      wangqin8207@163.com.
LA  - eng
GR  - 81500029/National Natural Science Foundation of China/
GR  - 81400029/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20190506
PL  - England
TA  - Respir Res
JT  - Respiratory research
JID - 101090633
RN  - 0 (CUL4A protein, human)
RN  - 0 (Cullin Proteins)
SB  - IM
EIN - Respir Res. 2023 Jul 14;24(1):188. PMID: 37452357
MH  - Aged
MH  - Cells, Cultured
MH  - Cullin Proteins/*biosynthesis
MH  - Epithelial-Mesenchymal Transition/*physiology
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Pulmonary Disease, Chronic Obstructive/*metabolism/pathology
MH  - Respiratory Mucosa/*metabolism/pathology
MH  - Retrospective Studies
PMC - PMC6501375
OTO - NOTNLM
OT  - CUL4A
OT  - Chronic obstructive pulmonary disease
OT  - Cigarette smoke
OT  - Epithelial-mesenchymal transition
OT  - Small airway epithelial cells
COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: The study was approved by the Medical 
      Ethics Committees of the Qilu Hospital, Shandong University (#: KYLL-2015-076). 
      CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare 
      that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains 
      neutral with regard to jurisdictional claims in published maps and institutional 
      affiliations.
EDAT- 2019/05/08 06:00
MHDA- 2019/12/25 06:00
PMCR- 2019/05/06
CRDT- 2019/05/08 06:00
PHST- 2019/02/11 00:00 [received]
PHST- 2019/04/14 00:00 [accepted]
PHST- 2019/05/08 06:00 [entrez]
PHST- 2019/05/08 06:00 [pubmed]
PHST- 2019/12/25 06:00 [medline]
PHST- 2019/05/06 00:00 [pmc-release]
AID - 10.1186/s12931-019-1048-4 [pii]
AID - 1048 [pii]
AID - 10.1186/s12931-019-1048-4 [doi]
PST - epublish
SO  - Respir Res. 2019 May 6;20(1):84. doi: 10.1186/s12931-019-1048-4.