Evidence map›Paper›PMID 39286973›Full record

ArticleThe Journal of clinical investigation2024

ADAMTS12 promotes fibrosis by restructuring extracellular matrix to enable activation of injury-responsive fibroblasts.

Konrad Hoeft, Lars Koch, Susanne Ziegler, Ling Zhang, Steffen Luetke, Maria C Tanzer, Debashish Mohanta, David Schumacher, Felix Schreibing, Qingqing Long and 21 more

Abstract read
In one paragraph

Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing 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

18 citing papers in PubMed.

  1. Review
  2. Macrophage-Fibroblast Crosstalk in Kidney Injury: A Narrative Review.International journal of molecular sciences · 2026
    Review
  3. Review
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  17. ECM remodelling by ADAMTS12 in fibrosis.Nature reviews. Nephrology · 2024
    Article
  18. 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

31 authors.

Konrad HoeftDepartment of Medicine 2 (Nephrology, Rheumatology, Clinical Immunology and Hypertension), RWTH Aachen University, Medical Faculty, Aachen, Germany.
Lars KochDepartment of Medicine 2 (Nephrology, Rheumatology, Clinical Immunology and Hypertension), RWTH Aachen University, Medical Faculty, Aachen, Germany.
Susanne ZieglerDepartment of Medicine 2 (Nephrology, Rheumatology, Clinical Immunology and Hypertension), RWTH Aachen University, Medical Faculty, Aachen, Germany.
Ling ZhangDepartment of Medicine 2 (Nephrology, Rheumatology, Clinical Immunology and Hypertension), RWTH Aachen University, Medical Faculty, Aachen, Germany.
Steffen LuetkeDepartment of Pediatrics and Adolescent Medicine.
Maria C TanzerThe Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
Debashish MohantaDepartment of Medicine 2 (Nephrology, Rheumatology, Clinical Immunology and Hypertension), RWTH Aachen University, Medical Faculty, Aachen, Germany.
David SchumacherDepartment of Medicine 2 (Nephrology, Rheumatology, Clinical Immunology and Hypertension), RWTH Aachen University, Medical Faculty, Aachen, Germany.
Felix SchreibingDepartment of Medicine 2 (Nephrology, Rheumatology, Clinical Immunology and Hypertension), RWTH Aachen University, Medical Faculty, Aachen, Germany.
Qingqing LongDepartment of Medicine 2 (Nephrology, Rheumatology, Clinical Immunology and Hypertension), RWTH Aachen University, Medical Faculty, Aachen, Germany.
Hyojin KimDepartment of Medicine 2 (Nephrology, Rheumatology, Clinical Immunology and Hypertension), RWTH Aachen University, Medical Faculty, Aachen, Germany.
Barbara M KlinkhammerInstitute of Pathology, RWTH Aachen University, Aachen, Germany.
Carla SchikarskiDepartment of Medicine 2 (Nephrology, Rheumatology, Clinical Immunology and Hypertension), RWTH Aachen University, Medical Faculty, Aachen, Germany.
Sidrah MaryamDepartment of Medicine 2 (Nephrology, Rheumatology, Clinical Immunology and Hypertension), RWTH Aachen University, Medical Faculty, Aachen, Germany.
Mathijs BaensCISTIM Leuven vzw, Leuven, Belgium.
Juliane HermannInstitute for Molecular Cardiovascular Research, RWTH Aachen University, Medical Faculty, Aachen, Germany.
Sarah KriegInstitute of Biochemistry and Molecular Biology, and.
Fabian PeiskerDepartment of Medicine 2 (Nephrology, Rheumatology, Clinical Immunology and Hypertension), RWTH Aachen University, Medical Faculty, Aachen, Germany.
Laura De LaporteInstitute of Technical and Macromolecular Chemistry, RWTH Aachen University, Aachen, Germany.
Gideon Jl SchaeferDepartment of Medicine 2 (Nephrology, Rheumatology, Clinical Immunology and Hypertension), RWTH Aachen University, Medical Faculty, Aachen, Germany.
Sylvia MenzelDepartment of Medicine 2 (Nephrology, Rheumatology, Clinical Immunology and Hypertension), RWTH Aachen University, Medical Faculty, Aachen, Germany.
Joachim JankowskiInstitute for Molecular Cardiovascular Research, RWTH Aachen University, Medical Faculty, Aachen, Germany.
Benjamin D HumphreysDivision of Nephrology, Department of Medicine, Washington University in St. Louis, St. Louis, Missouri, USA.
Adam WahidaInstitute of Metabolism and Cell Death, Helmholtz Zentrum München, Neuherberg, Germany.
Rebekka K SchneiderDepartment of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Matthias VerseleCISTIM Leuven vzw, Leuven, Belgium.
Peter BoorDepartment of Medicine 2 (Nephrology, Rheumatology, Clinical Immunology and Hypertension), RWTH Aachen University, Medical Faculty, Aachen, Germany.
Matthias MannMax-Planck Institute of Biochemistry, Martinsried, Germany.
Gerhard SengleDepartment of Pediatrics and Adolescent Medicine.
Sikander HayatDepartment of Medicine 2 (Nephrology, Rheumatology, Clinical Immunology and Hypertension), RWTH Aachen University, Medical Faculty, Aachen, Germany.
Rafael KramannDepartment of Medicine 2 (Nephrology, Rheumatology, Clinical Immunology and Hypertension), RWTH Aachen University, Medical Faculty, Aachen, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Fibrosis represents the uncontrolled replacement of parenchymal tissue with extracellular matrix (ECM) produced by myofibroblasts. While genetic fate-tracing and single-cell RNA-Seq technologies have helped elucidate fibroblast heterogeneity and ontogeny beyond fibroblast to myofibroblast differentiation, newly identified fibroblast populations remain ill defined, with respect to both the molecular cues driving their differentiation and their subsequent role in fibrosis. Using an unbiased approach, we identified the metalloprotease ADAMTS12 as a fibroblast-specific gene that is strongly upregulated during active fibrogenesis in humans and mice. Functional in vivo KO studies in mice confirmed that Adamts12 was critical during fibrogenesis in both heart and kidney. Mechanistically, using a combination of spatial transcriptomics and expression of catalytically active or inactive ADAMTS12, we demonstrated that the active protease of ADAMTS12 shaped ECM composition and cleaved hemicentin 1 (HMCN1) to enable the activation and migration of a distinct injury-responsive fibroblast subset defined by aberrant high JAK/STAT signaling.

Indexed as

Extracellular MatrixFibrosisMice, KnockoutADAMTS ProteinsAnimalsFibroblastsHumansMiceMyofibroblastsSignal TransductionADAMTS12 protein, humanAdamts12 protein, mouseADAMTS ProteinsCardiologyFibrosisNephrology

Identifiers

PMID39286973
PMCPMC11405035

What Socratic 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 Socratic graph.