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Cited by 459Autophagy in Disease and TherapyChronic Obstructive Pulmonary Disease (COPD) ResearchCalcium signaling and nucleotide metabolism

Egr-1 Regulates Autophagy in Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease

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Chen, Zhi-Hua, Kim, Hong Pyo, Sciurba, Frank C., Lee, Seon-Jin, Feghali-Bostwick, Carol, Stolz, Donna B., Dhir, Rajiv, Landreneau, Rodney J. +8 more·2008·PLoS ONE
DOI 10.1371/journal.pone.0003316PMC PMC2552992
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Abstract

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by abnormal cellular responses to cigarette smoke, resulting in tissue destruction and airflow limitation. Autophagy is a degradative process involving lysosomal turnover of cellular components, though its role in human diseases remains unclear. METHODOLOGY AND PRINCIPAL FINDINGS: Increased autophagy was observed in lung tissue from COPD patients, as indicated by electron microscopic analysis, as well as by increased activation of autophagic proteins (microtubule-associated protein-1 light chain-3B, LC3B, Atg4, Atg5/12, Atg7). Cigarette smoke extract (CSE) is an established model for studying the effects of cigarette smoke exposure in vitro. In human pulmonary epithelial cells, exposure to CSE or histone deacetylase (HDAC) inhibitor rapidly induced autophagy. CSE decreased HDAC activity, resulting in increased binding of early growth response-1 (Egr-1) and E2F factors to the autophagy gene LC3B promoter, and increased LC3B expression. Knockdown of E2F-4 or Egr-1 inhibited CSE-induced LC3B expression. Knockdown of Egr-1 also inhibited the expression of Atg4B, a critical factor for LC3B conversion. Inhibition of autophagy by LC3B-knockdown protected epithelial cells from CSE-induced apoptosis. Egr-1(-/-) mice, which displayed basal airspace enlargement, resisted cigarette-smoke induced autophagy, apoptosis, and emphysema. CONCLUSIONS: We demonstrate a critical role for Egr-1 in promoting autophagy and apoptosis in response to cigarette smoke exposure in vitro and in vivo. The induction of autophagy at early stages of COPD progression suggests novel therapeutic targets for the treatment of cigarette smoke induced lung injury.

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  • Several reports pointed out enhanced autophagy in COPD muscle, confirming data observed in the lung.

    “After that, several reports pointed out an enhanced autophagy in COPD muscle, confirming the data observed in the lung [180].”

    From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [180]

    The Results section, “Increased autophagy in human COPD lung tissues” (page unavailable), reports increased autophagy markers and autophagic vacuoles in COPD lung tissue. It does not report enhanced autophagy in COPD muscle or substantiate the claim that several reports found it there. (LLM, conf=0.88)

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  • Autophagy is increased in the lungs of COPD patients.

    “It is already established that autophagy is increased in the lungs of COPD patients [180].”

    From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [180]

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Authors
Chen, Z.-H., Kim, H. P., Sciurba, F. C., Lee, S.-J., Feghali-Bostwick, C., Stolz, D. B., Dhir, R., Landreneau, R. J., Schuchert, M. J., Yousem, S. A., Nakahira, K., Pilewski, J. M., Lee, J. S., Zhang, Y., Ryter, S. W., & Choi, A. M. K.
Affiliations
  • Brigham and Women's Hospital (US)
  • University of Pittsburgh (US)
Corresponding author
Choi, Augustine M. K.
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2008-10-02
Volume
3
Issue
10
Pages
e3316
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0003316
PMC
PMC2552992
OpenAlex
W2154846778
Cited by
459
References
4
Citations by year
2026: 4 · 2025: 18 · 2024: 15 · 2023: 22 · 2022: 21 · 2021: 27 · 2020: 30 · 2019: 29 · 2018: 35 · 2017: 44 · 2016: 37 · 2015: 35 · 2014: 25 · 2013: 33 · 2012: 27
FWCI
13.90
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • D-Scholarship@Pitt (University of Pittsburgh) (acceptedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • American Heart Association (HL60234)
  • National Institutes of Health (UL1TR000005, R01-HL55330)
  • National Heart, Lung, and Blood Institute (R01HL055330, P01-HL70807, R01HL55330, R01HL079904, R01HL60234, R01HL060234, P01HL070807, P50HL084948)
  • National Center for Advancing Translational Sciences
Topics
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
Keywords
EGR1, autophagy, chronic obstructive pulmonary disease, cigarette smoke, LC3B, histone deacetylase, E2F4, apoptosis, emphysema, lung epithelial cells, ATG4B, transcriptional regulation, lung injury
MeSH terms
Animals, Autophagy, Humans, Mice, Inbred C57BL, Smoking, Nicotiana, Apoptosis, Pulmonary Disease, Chronic Obstructive, Mice, Early Growth Response Protein 1

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