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Record W4414043704 · doi:10.1101/2025.09.02.673852

<i>Bigh3</i> is essential for pulmonary fibrosis

2025· preprint· en· W4414043704 on OpenAlexafffund
Anthony Altieri, Yashar Aghazadeh Habashi, Yein Chung, Erika E. McCartney, Ronen Schuster, Mark Abovsky, F. Abdullah, Shaheed W. Hakim, Sam Cooper, Igor Jurišica, Boris Hinz, Matthew B. Buechler

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Languageen
FieldMedicine
TopicInterstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
Canadian institutionsUniversity of Toronto
FundersNatural Sciences and Engineering Research Council of CanadaCanada First Research Excellence FundCanadian Institutes of Health ResearchHospital for Sick ChildrenUniversity of Toronto
KeywordsBleomycinPulmonary fibrosisLungFibrosisPathogenesisImmune systemIdiopathic pulmonary fibrosisKnockout mouse

Abstract

fetched live from OpenAlex

Abstract Transforming growth factor beta (TGF- β) -induced g ene- h uman, clone 3 (BIGH3) has been implicated as a biomarker of lung fibrosis. However, it is unknown if BIGH3 plays a functional role in fibrosis pathogenesis. To address this question, we used in silico , in vitro and in vivo approaches. We found that BIGH3 / Bigh3 is upregulated in human lung fibrosis and mouse models of pulmonary fibrosis. We next generated a novel Bigh3 knockout ( Bigh3 −/− ) mouse and found that while these animals exhibited lung architecture and immune cellularity that is broadly equivalent to wild-type mice, they were protected from lung fibrosis in response to bleomycin administration. In silico modeling suggested that BIGH3 can bind to integrin alpha v (ITGAV). In vitro co-culture systems revealed that activated human lung fibroblasts can elicit BIGH3 expression from human monocyte-derived macrophages. Last, macrophages elicited collagen expression from lung fibroblasts in a manner that is Bigh3 -dependent. Collectively, these data suggest that Bigh3 is a product of fibroblast-macrophage interactions that is essential for the pathogenesis of lung fibrosis, possibly via interactions with ITGAV.

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 score0.004
Threshold uncertainty score0.013

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0040.001

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 head0.010
GPT teacher head0.243
Teacher spread0.232 · 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
Published2025
Admission routes2
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicInterstitial Lung Diseases and Idiopathic Pulmonary Fibrosis→French-language works237,207→