Evidence map›Paper›PMID 24440594›Full record

ArticleFree radical biology & medicine2014

Nrf2 signaling modulates cigarette smoke-induced complement activation in retinal pigmented epithelial cells.

Lei Wang, Naoshi Kondo, Marisol Cano, Katayoon Ebrahimi, Takeshi Yoshida, Bradley P Barnett, Shyam Biswal, James T Handa

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Free radical biology & medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
9.1field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

60 citing papers in PubMed, 89 citations in OpenAlex.

  1. Complement C3 Activation in the Human Retinal Pigment Epithelium.Investigative ophthalmology & visual science · 2025
    Article
  2. Review
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  4. Extracellular Vesicles Derived from Adipose-Derived Mesenchymal Stem Cells Alleviate Apoptosis and Oxidative Stress of Retinal Pigment Epithelial Cells Through Activation of Nrf2 Signaling Pathway.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2024
    Article
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  6. Review
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  14. Proteostasis in aging-associated ocular disease.Molecular aspects of medicine · 2022
    Review
  15. Article
  16. Cell Death in AMD: The Rationale for Targeting Fas.Journal of clinical medicine · 2022
    Review
  17. Article
  18. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Lei WangWilmer Eye Institute, Johns Hopkins School of Medicine, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21287, USA.
Naoshi KondoWilmer Eye Institute, Johns Hopkins School of Medicine, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21287, USA.
Marisol CanoWilmer Eye Institute, Johns Hopkins School of Medicine, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21287, USA.
Katayoon EbrahimiWilmer Eye Institute, Johns Hopkins School of Medicine, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21287, USA.
Takeshi YoshidaWilmer Eye Institute, Johns Hopkins School of Medicine, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21287, USA.
Bradley P BarnettWilmer Eye Institute, Johns Hopkins School of Medicine, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21287, USA.
Shyam BiswalDepartment of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21287, USA.
James T HandaWilmer Eye Institute, Johns Hopkins School of Medicine, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21287, USA. Electronic address: jthanda@jhmi.edu.
Johns Hopkins University · US

Funding

Wilmer Core Grant for Vision ResearchP30EY001765 · NEI · JOHNS HOPKINS UNIVERSITY · PI Jiang Qian · 1985 to 2026
$22.1M
AGE-induced Phenotype of the Retinal Pigment EpitheliumR01EY014005 · NEI · JOHNS HOPKINS UNIVERSITY · PI HANDA, JAMES T · 2001 to 2015
$6.4M
Nrf2 signaling and oxidative stress in Age-related macular degenerationR01EY019904 · NEI · JOHNS HOPKINS UNIVERSITY · PI HANDA, JAMES T · 2010 to 2016
$4.1M
Regulation of Tumorigenesis and therapeutic resistance by Nrf2 in lung cancerR01CA140492 · NCI · JOHNS HOPKINS UNIVERSITY · PI BISWAL, SHYAM · 2010 to 2014
$1.8M
Developing Nrf2 as a target for treatment of corticosteroid resistance in COPDP50HL107169 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI BISWAL, SHYAM, WISE, ROBERT A. · 2011 to 2012
$911k
NCI NIH HHS R01 CA140492NCI NIH HHS R01CA140492NEI NIH HHS EY001765NEI NIH HHS EY019904NEI NIH HHS EY14005NEI NIH HHS P30 EY001765NEI NIH HHS R01 EY014005NEI NIH HHS R01 EY019904NHLBI NIH HHS P50 HL107169NHLBI NIH HHS P50HL107169
6 · The paper itself

Abstract

Whereas cigarette smoking (CS) and dysregulated complement are thought to play central roles in age-related macular degeneration (AMD), their exact roles are unknown. The aim of this study was to determine if CS activates complement and if the antioxidant transcription factor Nrf2 modulates this response. In AMD specimens, Nrf2 immunolabeling was strong in the cytoplasm, with scattered nuclear labeling of macular retinal pigmented epithelial (RPE) cells that appeared normal, but was decreased and without nuclear labeling in dysmorphic cells overlying drusen, a hallmark AMD lesion. Cigarette smoke extract (CSE) induced Nrf2 nuclear translocation in RPE cells with increased antioxidant and complement gene expression. Whereas CFH protein was not altered by CSE, the cell membrane regulator proteins CD46, CD55, and CD59 were decreased, and C3a and C3b, but not iC3b, were increased compared to controls. C5b-9 was increased by CSE, but at sublytic levels, only after addition of normal human serum. Nrf2 knockdown enhanced the increase in C3a and C3b from CSE, but not iC3b, C5a, or C5b-9. CSE also increased IL-1b expression and secretion after C3a generation and was reduced by a C3aR antagonist. In contrast, the Nrf2 activator CDDO-Im restored complement gene expression in RPE cells exposed to CSE. We provide evidence of altered Nrf2 in human AMD and that CSE induces a proinflammatory environment specifically by generating C3a and C3b, and Nrf2 deficiency magnifies this specific complement response.

Indexed as

Active Transport, Cell NucleusComplement ActivationEpithelial CellsFree RadicalsHumansImmunity, InnateMacular DegenerationNF-E2-Related Factor 2RetinaSignal TransductionSmokingFree RadicalsNFE2L2 protein, humanNF-E2-Related Factor 2Aging-related diseaseComplementFree radicalsInnate immunityNrf2Oxidative stress

Identifiers

PMID24440594
PMCPMC4006310
OpenAlexW2056337410

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.