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Record W3173756743 · doi:10.1096/fasebj.20.5.lb118-d

Lack of discoidin domain receptor 1 protects against lung fibrosis

2006· article· en· W3173756743 on OpenAlexafffundabout
Wolfgang F. Vogel

Bibliographic record

VenueThe FASEB Journal · 2006
Typearticle
Languageen
FieldMedicine
TopicCell Adhesion Molecules Research
Canadian institutionsCanada Research ChairsUniversity of TorontoUniversity of New Brunswick
FundersCanada Research Chairs
KeywordsDDR1Discoidin domainPulmonary fibrosisFibrosisMedicinePathologyBleomycinInflammationKnockout mouseMyofibroblastBronchoalveolar lavageLungImmunologyCancer researchReceptorReceptor tyrosine kinaseInternal medicine

Abstract

fetched live from OpenAlex

Rationale Discoidin Domain Receptor 1 (DDR1) is a tyrosine kinase activated by various types of collagen. Based on previous work showing increased DDR1 expression in bronchoalveolar lavage cells from patients with idiopathic pulmonary fibrosis, we hypothesized that DDR1 could be a key mediator during disease progression following lung injury. Objectives To investigate the response of DDR1 knockout and control mice to bleomycin‐induced lung injury. Methods Age‐ and gender‐matched C57/BL6 knockout and control mice received a single intratracheal instillation of 2U/kg bleomycin or saline, respectively. After 2 weeks, lung inflammation and fibrosis were assessed using immunohistochemistry, real time PCR, TUNEL assay, ELISA, FACS and Western blot analysis. Results Compared to control animals, DDR1‐null mice were largely protected against bleomycin injury. Collagen content as well as tenascin‐ C and fibrillin‐1 expression were significantly less increased in knockout than control mice. Myofibroblast expansion and apoptotic cell count were lower in DDR1‐null than control mice. Absence of inflammation in knockout mice was confirmed by lavage cell count and cytokine ELISA. Western blot analysis of injured lung tissue revealed that DDR1‐null mice failed to respond with an increase in p42/p44 and p38 MAPK pathway activation, which was observed in control mice. Conclusions Using a mouse strain lacking DDR1, our data provide compelling evidence that DDR1 expression is a prerequisite in the progression of lung inflammation and fibrosis. Blockade of DDR1 may therefore be a novel and attractive therapeutic intervention in patients with pulmonary fibrosis. Grant support: Canada Research Chair Program

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.027
GPT teacher head0.304
Teacher spread0.277 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2006
Admission routes3
Has abstractyes

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