Evidence map›Paper›PMID 25951185›Full record

ArticlePloS one2015

Overexpression of Telomerase Protects Human and Murine Lung Epithelial Cells from Fas- and Bleomycin-Induced Apoptosis via FLIP Upregulation.

Nissim Arish, Pazit Y Cohen, Regina Golan-Gerstl, Zvi Fridlender, Mark Richter Dayan, Philip Zisman, Raphael Breuer, Shulamit B Wallach-Dayan

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.8field-weighted citation impact, top 29% 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

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. 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 3 institutions in 2 countries.

Nissim ArishLaboratory for Lung Cellular & Molecular Biology, Institute of Pulmonary Medicine, Hadassah - Hebrew University Medical Center, Jerusalem, Israel.
Pazit Y CohenLaboratory for Lung Cellular & Molecular Biology, Institute of Pulmonary Medicine, Hadassah - Hebrew University Medical Center, Jerusalem, Israel.
Regina Golan-GerstlLaboratory for Lung Cellular & Molecular Biology, Institute of Pulmonary Medicine, Hadassah - Hebrew University Medical Center, Jerusalem, Israel.
Zvi FridlenderLaboratory for Lung Cellular & Molecular Biology, Institute of Pulmonary Medicine, Hadassah - Hebrew University Medical Center, Jerusalem, Israel; Department of Pulmonary and Critical Care Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, United States of America.
Mark Richter DayanDepartment of Emergency Medicine, Shaare Zedek Medical Center, Jerusalem, Israel.
Philip ZismanLaboratory for Lung Cellular & Molecular Biology, Institute of Pulmonary Medicine, Hadassah - Hebrew University Medical Center, Jerusalem, Israel.
Raphael BreuerLaboratory for Lung Cellular & Molecular Biology, Institute of Pulmonary Medicine, Hadassah - Hebrew University Medical Center, Jerusalem, Israel; Department of Pathology, Boston University School of Medicine, Boston, MA, United States of America.
Shulamit B Wallach-DayanLaboratory for Lung Cellular & Molecular Biology, Institute of Pulmonary Medicine, Hadassah - Hebrew University Medical Center, Jerusalem, Israel.
Hadassah Medical Center · ILBoston University · USShaare Zedek Medical Center · IL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

High doses of bleomycin administered to patients with lymphomas and other tumors lead to significant lung toxicity in general, and to apoptosis of epithelial cells, in particular. Apoptosis of alveolar epithelium is an important step in the pathogenesis of bleomycin-induced pulmonary fibrosis. The Fas-FasL pathway is one of the main apoptotic pathways involved. Telomerase is a ribonucleoprotein RNA-dependent DNA polymerase complex consisting of an RNA template and a catalytic protein, telomerase reverse transcriptase (TERT). Telomerase also possess extra-telomeric roles, including modulation of transcription of anti-apoptotic genes, differentiation signals, and more. We hypothesized that telomerase overexpression affects Fas-induced epithelial cell apoptosis by an extra-telomeric role such as regulation of anti-apoptotic genes, specifically FLICE-like inhibitory protein (FLIP). Telomerase in mouse (MLE) and human (A549) lung epithelial cell lines was upregulated by transient transfection using cDNA hTERT expression vector. Telomerase activity was detected using a real-time PCR-based system. Bleomycin, and bleomycin-induced Fas-mediated apoptosis following treatment with anti-Fas activating mAb or control IgG, were assessed by Annexin V staining, FACS analysis, and confocal microscopy; caspase cleavage by Western blot; FLIP or Fas molecule detection by Western blot and flow cytometry. hTERT transfection of lung epithelial cells resulted in a 100% increase in their telomerase activity. Fas-induced lung epithelial cell apoptosis was significantly reduced in hTERT-transfected cells compared to controls in all experiments. Lung epithelial cells with increased telomerase activity had higher levels of FLIP expression but membrane Fas expression was unchanged. Upregulation of hTERT+ in human lung epithelial cells and subsequent downregulation of FLIP by shFLIP-RNA annulled hTERT-mediated resistance to apoptosis. Telomerase-mediated FLIP overexpression may be a novel mechanism to confer protection from apoptosis in bleomycin-exposed human lung epithelial cells.

Indexed as

AnimalsAntibiotics, AntineoplasticApoptosisBleomycinCASP8 and FADD-Like Apoptosis Regulating ProteinCell LineEpithelial Cellsfas ReceptorHumansLungMiceTelomeraseTransfectionUp-RegulationAntibiotics, AntineoplasticBleomycinCASP8 and FADD-Like Apoptosis Regulating ProteinCFLAR protein, humanfas ReceptorTelomerase

Identifiers

PMID25951185
PMCPMC4423936
OpenAlexW334205349

What OpenQuestion holds

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LicenceCC BY
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.