Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Respiratory Research
Published in: Respiratory Research 1/2018

Open Access 01-12-2018 | Research

miR-34a is involved in CSE-induced apoptosis of human pulmonary microvascular endothelial cells by targeting Notch-1 receptor protein

Authors: Ying-Jiao Long, Xiao-Peng Liu, Shan-Shan Chen, Dan-Dan Zong, Yan Chen, Ping Chen

Published in: Respiratory Research | Issue 1/2018

Login to get access

Abstract

Background

Abnormal apoptosis of lung endothelial cells has been observed in emphysematous lung tissue and has been suggested to be an important upstream event in the pathogenesis of chronic obstructive pulmonary disease (COPD). Studies have shown that microRNAs (miRNAs) contribute to the pathogenesis of pulmonary diseases by regulating cell apoptosis. The present study was designed to investigate the expression of microRNA-34a (miR-34a) in human pulmonary microvascular endothelial cells (HPMECs) exposed to cigarette smoke extract (CSE), and the potential regulatory role of miR-34a in endothelial cell apoptosis.

Results

Our results showed that the expression of miR-34a was significantly increased in CSE-treated HPMECs, and inhibiting miR-34a attenuated CSE-induced HPMEC apoptosis. Furthermore, expression of Notch-1, a receptor protein in the Notch signalling pathway, was decreased and was inversely correlated with miR-34a expression in HPMECs treated with CSE. Computational miRNA target prediction confirmed that Notch-1 is a target of miR-34a. Luciferase reporter assay further confirmed the direct interaction between miR-34a and the 3’-untranslated region (UTR) of Notch-1. Restoration of Notch-1 pathway was able to partially block the effect of miR-34a on HPMEC apoptosis. These results indicate that Notch-1 is a critical downstream target of miR-34a in regulating the CSE-induced HPMEC apoptosis.

Conclusions

Our results suggest that miR-34a plays a key role in CSE-induced endothelial cell apoptosis by directly regulating its target gene Notch-1 in endothelial cells.
Literature
1.
2.
3.
Yang M, Chen P, Peng H, et al. Cigarette smoke extract induces aberrant cytochrome-c oxidase subunit II methylation and apoptosis in human umbilical vascular endothelial cells. Am J Physiol Cell Physiol. 2015;308:C378–84.CrossRefPubMed
4.
5.
Yokohori N, Aoshiba K, Nagai A. Increased levels of cell death and proliferation in alveolar wall cells in patients with pulmonary emphysema. Chest. 2004;125:626–32.CrossRefPubMed
6.
Aoshiba K, Yokohori N, Nagai A. Alveolar wall apoptosis causes lung destruction and emphysematous changes. Am J Respir Cell Mol Biol. 2003;28:555–62.CrossRefPubMed
7.
Petrache I, Fijalkowska I, Zhen L, et al. A novel antiapoptotic role for alpha1-antitrypsin in the prevention of pulmonary emphysema. Am J Respi Crit Care Med. 2006;173:1222–8.CrossRef
8.
Shan C, Ping C, Zhang C, et al. Oral N-acetylcysteine attenuates pulmonary emphysema and alveolar septal cell apoptosis in smoking-induced COPD in rats. Respirology. 2009;14:354–9.CrossRef
9.
Liu SK, Chen P, Apoptosis CJB. Of alveolar epithelial cells and pulmonary vascular endothelial cells in chronic obstructive pulmonary disease. Zhonghua Jie He He Hu Xi Za Zhi. 2008;31:581–5.PubMed
10.
Chen Y, Luo H, Kang N, et al. Beraprost sodium attenuates cigarette smoke extract-induced apoptosis in vascular endothelial cells. Mol Biol Rep. 2012;39:10447–57.CrossRefPubMed
11.
Izzotti A, Calin GA, Arrigo P, et al. Downregulation of microRNA expression in the lungs of rats expose to cigarette smoke. FASEBJ. 2009;23:806–12.CrossRef
12.
13.
Kara M, Kirkil G, Kalemci S. Differential expression of microRNAs in chronic obstructive pulmonary disease. Adv Clin Exp Med. 2016;25:21–6.CrossRefPubMed
14.
Mizuno S, Bogaard HJ, Gomez-Arroyo J, et al. MicroRNA-199a-5p is associated with hypoxia-inducible factor-1a expression in lungs from patients with COPD. Chest. 2012;142:663–72.CrossRefPubMedPubMedCentral
15.
Mizuno S, Yasuo M, Bogaard HJ, et al. Inhibiton of histone deacetylase causes emphysema. Am J Physiol Lung Cell Mol Physiol. 2011;300:L402–13.CrossRefPubMed
16.
Chang TC, Wentzel EA, Kent OA, et al. Transactivation of miR-34a by p53 broadly influence gene expression and promotes apoptosis. Mol Cell. 2007;26:745–52.CrossRefPubMedPubMedCentral
17.
Welch C, Chen Y, Stallings RL. MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells. Oncogene. 2007;26:5017–22.CrossRefPubMed
18.
Kumar B, Yadav A, Lang J, Teknos TN, Kumar P. Dysregulation of microRNA-34a expression in head and neck squamous cell carcinoma promotes tumor growth and tumor angiogenesis. PLoS One. 2012;7:e37601.CrossRefPubMedPubMedCentral
19.
Richter A, O’Donnell RA, Powell RM, et al. Autocrine ligands for the epidermal growth factor receptor mediate interleukin-8 release from bronchial epithelial cells in response to cigarette smoke. Am J Respir Cell Mol Biol. 2002;27:85–90.CrossRefPubMed
20.
Wael H, Yoshida R, Kudoh S, et al. Notch1 signaling controls cell proliferation, apoptosis and differentiation in lung carcinoma. Lung Cancer. 2014;85:131–40.CrossRefPubMed
21.
Comer DM, Elborn JS, Ennis M. Inflammatory and cytotoxic effects of acrolein, nicotine, acetylaldehyde and cigarette smoke extract on human nasal epithelial cells. BMC Pulm Med. 2014;14(32)
22.
Zhang C, Cai S, Chen P, et al. Inhibition of TNF-α reduces alveolar septal cell apoptosis in passive smoking rats. Chin Med J. 2008;121:597–601.PubMed
23.
He S, He Z, Chen Y, et al. C-kit/c-kit ligand interaction of bone marrow endothelial progenitor cells is influenced in a cigarette smoke extract-induced emphysema model. Exp Lung Res. 2013;39:258–67.CrossRefPubMed
24.
Carnevali S, Petruzzelli S, Longoni B, et al. Cigarette smoke extract induces oxidative stress and apoptosis in human lung fibroblasts. Am J Physiol Lung Cell Mol Physiol. 2003;284:L955–63.CrossRefPubMed
25.
Ruta A, Mark B, Edward B, et al. Nuclear localization of active matrix metalloproteinase-2 in cigarette smoke-exposed apoptotic endothelial cells. Exp Lung Res. 2009;35:59–75.CrossRefPubMed
26.
Aoshiba K, Tamaoki J, Nagai A. Acute cigarette smoke exposure induces apoptosis of alveolar macrophages. Am J Physiol Lung Cell Mol Physiol. 2001;281:L1392–401.CrossRefPubMed
27.
28.
Akbas F, Coskunpinar E, Aynaci E, et al. Analysis of serum microRNAs as potential biomarker in chronic obstructive pulmonary disease. Exp Lung Res. 2012;38:286–94.CrossRefPubMed
29.
Molina-Pinelo D, Pastor MD, Suarez R, et al. MicroRNA clusters: dysregulation in lung adenocarcinoma and COPD. Eur Respir J. 2014;43:1740–9.CrossRefPubMed
30.
Zhao Y, Xu Y, Li Y, et al. NF-KB mediated inflammation leading to EMT via miR-200c is involved in cell transformation induced by cigarette smoke extract. Toxicol Sci. 2013;135:265–76.CrossRefPubMed
31.
Oldenburger A, van Basten B, Kooistra W, et al. Interaction between Epac1 and miRNA-7 in airway smooth muscle cells. Naunyn Schmiedeberg's Arch Pharmacol. 2014;387:795–7.CrossRef
32.
33.
Wang G, Wang R, Strulovici-Barel Y, et al. Persistence of smoking induced dysregulation of miRNA expression in the small airway epithelium despite smoking cessation. PLoS One. 2015;10:e0120824.CrossRefPubMedPubMedCentral
34.
35.
Ke L, Huang J, Xie M, et al. MiR-34a regulates autophagy and apoptosis by targeting HMGB1 in the retinoblastoma cell. Autophagy. 2014;10:442–52.CrossRef
36.
37.
Pang RT, Leung CO, Ye TM, et al. MicroRNA-34a suppresses invasion though downregulation of Notch1 and Jagged1 in cervical carcinoma and choriocarcinoma cells. Carcingenesis. 2010;31:1037–44.CrossRef
38.
Artavanis-Tsakonas S, Rand MD, Lake RJ. Notch signaling: cell fate control and signal integration in development. Science. 1999;284:770–6.CrossRefPubMed
39.
Tsao PN, Vasconcelos M, Izvolsky KI, et al. Notch1 signaling controls the balance of ciliated and secretory cell fates in developing airways. Development. 2009;136:2297–307.CrossRefPubMedPubMedCentral
40.
Roca C, Adams RH. Regulation of vascular morphogenesis by notch signaling. Genes Dev. 2007;21:2511–24.CrossRefPubMed
41.
Tilley AE, Harvey BG, Heguy A, et al. Down-regulation of the notch pathway in human airway epithelium in association with smoke and chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2009;179:457–66.CrossRefPubMed
42.
Jiang JH, Zeng HH, Zong DD, Peng H, Chen P. Different expression of Notch receptor in lung tissue of COPD and its relationship with pulmonary endothelial cells apoptosis [A]. 2013 Annual congress of Chinese thoracic society [C]. Da Lian: Chinese medical association, 2013;pp.171.
43.
Rangarajan A, Syal R, Selvarajah S, et al. Activated Notch1 signaling cooperates with papillomavirus oncogenes in transformation and generates resistance to apoptosis on matrix withdrawal through PKB/Akt. Virology. 2001;286:23–30.CrossRefPubMed
44.
Nair P, Somasundaram K, Krishna S. Activated Notch1 inhibits p53-induced apoptosis and sustains transformation by human papillomavirus type 16 E6 and E7 oncogenes through a PO3K-PKB/Akt-dependent pathway. J Virol. 2003;77:7106–12.CrossRefPubMedPubMedCentral
45.
Jehn BM, Bielke W, Pear WS, et al. Cutting edge: protective effects of notch-1 on TCR-induced apoptosis. J Immunol. 1999;162:635–8.PubMed
46.
47.
Li WB, Ma MW, Dong LJ, et al. MicroRNA-34a targets notch1 and inhibits cell proliferation in glioblastoma multiforme. Cancer Biol Ther. 2011;12:477–83.CrossRefPubMed
48.
Ji X, Wang Z, Geamanu A, et al. Delta-tocotrienol suppresses Notch-1 pathway by upregulating miR-34a in nonsmall cell lung cancer cells. Int J Cancer. 2012;131:2668–77.CrossRefPubMedPubMedCentral
49.
50.
Mungamuri SK, Yang X, Thor AD, Somasundaram K. Survival signalling by Notch1: mammalian target of rapamycin (mTOR)-dependent inhibition of p53. Cancer Res. 2006;66:4715–24.CrossRefPubMed
51.
Qi R, An H, Yu Y, et al. Notch1 signaling inhibits growth of human hepatocellular carcinoma through induction of cell cycle arrest and apoptosis. Cancer Res. 2003;63:8323–9.PubMed
52.
Yang X, Klein R, Tian X, et al. Notch activation induces apoptosis in neural progenitor cells through a p53-dependent pathway. Dev Biol. 2004;269:81–94.CrossRefPubMed
53.
Dotto GP. Crosstalk of notch with p53 and p63 in cancer growth control. Nat Rev Cancer. 2009;9:587–95.CrossRefPubMed
54.
Rangarajan A, Talora C, Okuyama R, et al. Notch signaling is a direct determinant of keratinocyte growth arrest and entry into differentiation. EMBO J. 2001;20:3427–36.CrossRefPubMedPubMedCentral
55.
Metadata
Title
miR-34a is involved in CSE-induced apoptosis of human pulmonary microvascular endothelial cells by targeting Notch-1 receptor protein
Authors
Ying-Jiao Long
Xiao-Peng Liu
Shan-Shan Chen
Dan-Dan Zong
Yan Chen
Ping Chen
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2018
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-018-0722-2

Other articles of this Issue 1/2018

Respiratory Research 1/2018 Go to the issue

Research

Immunohistological features related to functional impairment in lymphangioleiomyomatosis

Research

Indacaterol/glycopyrronium versus salmeterol/fluticasone in the prevention of clinically important deterioration in COPD: results from the FLAME study

Research

Cytotoxic lymphocytes in COPD airways: increased NK cells associated with disease, iNKT and NKT-like cells with current smoking

Research

FK506-binding protein 10 (FKBP10) regulates lung fibroblast migration via collagen VI synthesis

Research

Dihydrotestosterone is a predictor for mortality in males with community-acquired pneumonia: results of a 6-year follow-up study

Research

A candidate gene identification strategy utilizing mouse to human big-data mining: “3R-tenet” in COPD genetic research

ACC 2024 Congress Coverage

Cardiology Video

Highlights from the ACC 2024 Congress

Watch now

Watch official videos from the ACC congress summarizing key highlights from the last year in heart failure, cardiomyopathies, valvular disease, pulmonary vascular disease, and pediatric cardiology.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits