Evidence map›Paper›PMID 28629363›Full record

ArticleRespiratory research2017

Fibroblast paracrine TNF-α signaling elevates integrin A5 expression in idiopathic pulmonary fibrosis (IPF).

Gali Epstein Shochet, Elizabetha Brook, Lilach Israeli-Shani, Evgeny Edelstein, David Shitrit

Open access · goldAbstract read
In one paragraph

Article in Respiratory research, 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
2.9field-weighted citation impact, top 9% 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, 62 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. Review
  12. Article
  13. Risk factors and management of lung cancer in idiopathic pulmonary fibrosis: A comprehensive review.Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG · 2025
    Article
  14. The role of vascularity and the fibrovascular interface in interstitial lung diseases.European respiratory review : an official journal of the European Respiratory Society · 2025
    Review
  15. Article
  16. Article
  17. Review
  18. Prostaglandin E2 (PGE2) and Roflumilast Involvement in IPF Progression.International journal of molecular sciences · 2023
    Review
  19. Review
  20. Multicellular network analysis of melanoma heterogeneity by scRNA-seq.American journal of translational research · 2023
    Article
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

5 authors at 2 institutions in 1 country.

Gali Epstein ShochetPulmonary Department, Meir Medical Center, 59 Tchernichovsky St, Kfar Saba, 44281, Israel. gali.epstein@clalit.org.il.
Elizabetha BrookSackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Lilach Israeli-ShaniPulmonary Department, Meir Medical Center, 59 Tchernichovsky St, Kfar Saba, 44281, Israel.
Evgeny EdelsteinSackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
David ShitritPulmonary Department, Meir Medical Center, 59 Tchernichovsky St, Kfar Saba, 44281, Israel.
Tel Aviv University · ILMeir Medical Center · IL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIdiopathic pulmonary fibrosis (IPF) is a progressive lung disease with a poor prognosis. Inflammatory cytokines play a significant role in IPF pathology. However, the fibroblast itself is also believed to be the primary effector in IPF. We hypothesized that the fibroblasts themselves secrete pro-inflammatory cytokines that could propagate IPF by affecting normal neighboring cells. Thus, we explored the effects of IPF fibroblast derived media on normal fibroblast characteristics.

methodsPrimary IPF/normal tissue derived fibroblast cultures were established and their supernatants were collected (IPF/N-SN, respectively). These supernatants were added to normal fibroblasts. Cell death (caspase-3, western blot), proliferation, viability (WST-1), migration (scratch test) and cell detachment (crystal violet and fibronectin adhesion assays) were tested. 10 inflammatory cytokines were measured by ELISA-based quantitative array. Integrin α5 (ITGA5), pIκBα, p/total STAT3 levels were measured by western blot/IHC. TNF-α involvement was confirmed using Infliximab ®, anti-TNF-α mAb.

resultsThe IPF-SN facilitated fibroblast cell detachment and reduced cell migration (p < 0.05). Nevertheless, these effects were reversed when cells were seeded on fibronectin. The exposure to the IPF-SN also elevated ITGA5 levels, the fibronectin receptor, in addition to NFκB pathway activation (pIκBα↑ 150%, p < 0.05). In accordance, IPF derived fibroblasts were found to express higher ITGA5 than the normal cells (44%↑, p < 0.05). ITGA5 was also expressed in the fibroblastic foci. The IPF-SN contained high TNF-α levels (3-fold, p < 0.05), and Infliximab pretreatment successfully reversed all the above observations.

conclusionWe suggest a possible mechanism in which IPF fibroblast secreted TNF-α modifies neighboring fibroblast cell behavior.

Indexed as

Cells, CulturedFibroblastsGene ExpressionHumansIdiopathic Pulmonary FibrosisIntegrin alpha5Paracrine CommunicationTumor Necrosis Factor-alphaIntegrin alpha5Tumor Necrosis Factor-alphaFibroblastsIdiopathic pulmonary fibrosis (IPF)Integrin α5TNF-α

Identifiers

PMID28629363
PMCPMC5477311
OpenAlexW2655242042

What OpenQuestion holds

Textmetadata
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.