Evidence map›Paper›PMID 40634525›Full record

ArticleCommunications biology2025

Triggering AHR resolves TGF-β1 induced fibroblast activation and promotes AT1 cell regeneration in alveolar organoids.

Andrew S Hagan, Scott Williams, Casey J N Mathison, Shanshan Yan, Bao Nguyen, Glenn C Federe, Guray Kuzu, Joseph C Siefert, Janice Hampton, Victor Chichkov and 9 more

Abstract read
In one paragraph

Article in Communications biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
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

8 citing papers in PubMed.

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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

19 authors.

Andrew S HaganNovartis Biomedical Research, San Diego, CA, USA.ORCID http://orcid.org/0000-0003-2265-3355
Scott WilliamsNovartis Biomedical Research, San Diego, CA, USA.
Casey J N MathisonNovartis Biomedical Research, San Diego, CA, USA.ORCID http://orcid.org/0000-0002-1310-826X
Shanshan YanNovartis Biomedical Research, San Diego, CA, USA.
Bao NguyenNovartis Biomedical Research, San Diego, CA, USA.
Glenn C FedereNovartis Biomedical Research, San Diego, CA, USA.
Guray KuzuNovartis Biomedical Research, San Diego, CA, USA.
Joseph C SiefertNovartis Biomedical Research, San Diego, CA, USA.
Janice HamptonNovartis Biomedical Research, San Diego, CA, USA.
Victor ChichkovNovartis Biomedical Research, San Diego, CA, USA.
S Whitney BarnesNovartis Biomedical Research, San Diego, CA, USA.
Frederick J KingNovartis Biomedical Research, San Diego, CA, USA.ORCID http://orcid.org/0000-0001-5958-5451
Brandon L TaylorNovartis Biomedical Research, San Diego, CA, USA.
John R WalkerNovartis Biomedical Research, San Diego, CA, USA.
Rui ZhaoNovartis Biomedical Research, San Diego, CA, USA.
Jimmy ElliottNovartis Biomedical Research, San Diego, CA, USA.
Dean P PhillipsNovartis Biomedical Research, San Diego, CA, USA.ORCID http://orcid.org/0009-0001-8944-4139
Bin FangNovartis Biomedical Research, San Diego, CA, USA. bin.fang@novartis.com.ORCID http://orcid.org/0009-0002-3245-1626
Rebekah S DeckerNovartis Biomedical Research, San Diego, CA, USA. rebekah.decker@novartis.com.ORCID http://orcid.org/0009-0007-3727-4784

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Regeneration of the alveolar epithelium is necessary to restore tissue architecture and gas exchange capabilities in chronic pulmonary diseases such as fibrosing interstitial lung disease. While it is known alveolar type 2 (AT2) cells give rise to alveolar type 1 (AT1) cells to repair the alveolar epithelium after injury, methods to promote this process under pathological settings are poorly understood. Here, using a complex 3D organoid culture with TGF-β1 dependent impaired AT1 spheroid formation, we performed a high-throughput screen (HTS) with ~16,800 compounds to identify small molecules that increase number of AT1 spheroids. Longitudinal single cell RNA sequencing (scRNA-seq) revealed that DB-11-BE87 increased AT1 regeneration by reducing TGF-β1 induced fibroblast activation, concurrently with AHR activation in those cells. These studies highlight a HTS system to identify factors that can promote AT1 differentiation and suggest AHR activation as a method to counteract pathological TGF-β1 signaling in pulmonary disease.

Indexed as

Alveolar Epithelial CellsBasic Helix-Loop-Helix ProteinsFibroblastsOrganoidsPulmonary AlveoliReceptors, Aryl HydrocarbonRegenerationTransforming Growth Factor beta1AnimalsCell DifferentiationHumansMiceSignal TransductionBasic Helix-Loop-Helix ProteinsReceptors, Aryl HydrocarbonTransforming Growth Factor beta1

Identifiers

PMID40634525
PMCPMC12241620

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.