Evidence mapPaperPMID 28855674Full record

ArticleScientific reports2017

Src-dependent EGFR transactivation regulates lung inflammation via downstream signaling involving ERK1/2, PI3Kδ/Akt and NFκB induction in a murine asthma model.

Ahmed Z El-Hashim, Maitham A Khajah, Waleed M Renno, Rhema S Babyson, Mohib Uddin, Ibrahim F Benter, Charles Ezeamuzie, Saghir Akhtar

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
3.6field-weighted citation impact, top 7% 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

45 citing papers in PubMed, 72 citations in OpenAlex.

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  15. Role of mucociliary clearance system in respiratory diseases.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2023
    Article
  16. Article
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  19. Anti-inflammatory mechanism of rhein in treating asthma based on network pharmacology.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2022
    Article
  20. Review
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 3 countries.

Ahmed Z El-HashimDepartment of Pharmacology & Therapeutics, Faculty of Pharmacy, Kuwait City, Kuwait. ahmed.elhashim@hsc.edu.kw.
Maitham A KhajahDepartment of Pharmacology & Therapeutics, Faculty of Pharmacy, Kuwait City, Kuwait.
Waleed M RennoDepartment of Anatomy, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait.
Rhema S BabysonDepartment of Pharmacology & Therapeutics, Faculty of Pharmacy, Kuwait City, Kuwait.
Mohib UddinRespiratory, Inflammation & Autoimmunity iMED, AstraZeneca R&D Gothenburg, Mölndal, Sweden.
Ibrahim F BenterFaculty of Medicine, Eastern Mediterranean University, Famagusta, Cyprus.
Charles EzeamuzieDepartment of Pharmacology & Toxicology, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait.
Saghir AkhtarDepartment of Pharmacology & Toxicology, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait.
Kuwait University · KWAstraZeneca (Sweden) · SEEastern Mediterranean University · CY

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The molecular mechanisms underlying asthma pathogenesis are poorly characterized. In this study, we investigated (1) whether Src mediates epidermal growth factor receptor (EGFR) transactivation; (2) if ERK1/2, PI3Kδ/Akt and NF-κB are signaling effectors downstream of Src/EGFR activation; and (3) if upstream inhibition of Src/EGFR is more effective in downregulating the allergic inflammation than selective inhibition of downstream signaling pathways. Allergic inflammation resulted in increased phosphorylation of EGFR, Akt, ERK1/2 and IκB in the lung tissues from ovalbumin (OVA)-challenged BALB/c mice. Treatment with inhibitors of Src (SU6656) or EGFR (AG1478) reduced EGFR phosphorylation and downstream signaling which resulted in the inhibition of the OVA-induced inflammatory cell influx in bronchoalveolar lavage fluid (BALF), perivascular and peribronchial inflammation, fibrosis, goblet cell hyper/metaplasia and airway hyper-responsiveness. Treatment with pathway-selective inhibitors for ERK1/2 (PD89059) and PI3Kδ/Akt (IC-87114) respectively, or an inhibitor of NF-κB (BAY11-7085) also reduced the OVA-induced asthmatic phenotype but to a lesser extent compared to Src/EGFR inhibition. Thus, Src via EGFR transactivation and subsequent downstream activation of multiple pathways regulates the allergic airway inflammatory response. Furthermore, a broader upstream inhibition of Src/EGFR offers an attractive therapeutic alternative in the treatment of asthma relative to selectively targeting the individual downstream signaling effectors.

Indexed as

Transcriptional ActivationAnimalsAsthmaBronchoalveolar Lavage FluidDown-RegulationErbB ReceptorsHumansIndolesMaleMAP Kinase Signaling SystemMiceMice, Inbred BALB CNF-kappa BOvalbuminPhosphorylationProto-Oncogene Proteins pp60(c-src)EGFR protein, humanErbB ReceptorsIndolesNF-kappa BOvalbuminProto-Oncogene Proteins pp60(c-src)QuinazolinesRTKI cpdSU 6656SulfonamidesTyrphostins

Identifiers

PMID28855674
PMCPMC5577320
OpenAlexW2745969995

What Socratic holds

Textmetadata
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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 Socratic graph.