Evidence map›Paper›PMID 41629266›Full record

ArticleSignal transduction and targeted therapy2026

Wnt-associated DKK3 in keratinocytes mediates radiation-induced hyperplasia, dermatitis and skin fibrosis.

Li Li, Ramon Lopez Perez, Khuram Shehzad, Richard Jennemann, Claudia Schmidt, Thomas Walle, Alexandra Tietz-Dahlfuß, Elisabeth Grimm, Joscha A Kraske, Peter Häring and 23 more

Abstract read
In one paragraph

Article in Signal transduction and targeted therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Review
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

33 authors.

Li LiMolecular Radiooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Ramon Lopez PerezMolecular Radiooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Khuram ShehzadClinical Biochemistry, Internal Medicine IV, LMU University Hospital, Munich, Germany.
Richard JennemannResearch Group Lipid Pathobiochemistry, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Claudia SchmidtLight Microscopy Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Thomas WalleMolecular Radiooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0003-4835-955X
Alexandra Tietz-DahlfußMolecular Radiooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Elisabeth GrimmResearch Group Lipid Pathobiochemistry, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Joscha A KraskeMolecular Radiooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0002-8567-6020
Peter HäringMedical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Uladzimir BarayeuFaculty of Biosciences, Heidelberg University, Heidelberg, Germany.ORCID http://orcid.org/0000-0001-8426-166X
Tobias P DickFaculty of Biosciences, Heidelberg University, Heidelberg, Germany.
Luxi YeMolecular Radiooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Stephan A BraunDept. of Dermatology, University Hospital Münster, University of Münster, Münster, Germany.
Michael HertlDept. of Dermatology and Allergy, University Clinics Marburg, Marburg, Germany.
Thomas WorzfeldInstitute of Pharmacology, Marburg University, Marburg, Germany.
Thorsten WiechNephropathology University Clinics Hamburg-Eppendorf (UKE Hamburg), Hamburg, Germany.
Huihui JiDept. of Pathology, School of Basic Medical Sciences, Peking University Third Hospital, Peking University Health Science Center, Beijing, China.
Jing SuDept. of Pathology, School of Basic Medical Sciences, Peking University Third Hospital, Peking University Health Science Center, Beijing, China.
Jonathan M SchneeweissMolecular Radiooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.ORCID http://orcid.org/0009-0004-6934-7501
Muzi LiuMolecular Radiooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Katharina KommossChronic Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0003-2428-2658
Matthias HeikenwälderChronic Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Bingwen ZouMolecular Radiooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.ORCID http://orcid.org/0000-0002-0825-3657
Sabrina MücklichDept. of Dermatology, University Hospital Münster, University of Münster, Münster, Germany.
Kerstin SteinbrinkDept. of Dermatology, University Hospital Münster, University of Münster, Münster, Germany.
Verena K RakerDept. of Dermatology, University Hospital Münster, University of Münster, Münster, Germany.ORCID http://orcid.org/0000-0001-7264-0371
Wenjun WuMolecular Radiooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Elfriede NoessnerImmunoanalytics-Tissue Control Immunocytes, Helmholtz Center, Munich, Germany.
Hermann-Josef GröneInstitute of Pharmacology, Marburg University, Marburg, Germany.
Peter J Nelson *Clinical Biochemistry, Internal Medicine IV, LMU University Hospital, Munich, Germany. peter.nelson@med.uni-muenchen.de.
Roger Sandhoff *Research Group Lipid Pathobiochemistry, German Cancer Research Center (DKFZ), Heidelberg, Germany. r.sandhoff@dkfz.de.ORCID http://orcid.org/0000-0003-3794-9458
Peter E Huber *Molecular Radiooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany. p.huber@dkfz.de.ORCID http://orcid.org/0000-0002-4811-300X

Funding

Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research) BMBF/BMU: 03NUK004A,CChina Scholarship Council (CSC) Research GrantDeutsche Forschungsgemeinschaft (German Research Foundation) SFB1009 B11-194468054Deutsche Forschungsgemeinschaft (German Research Foundation) SFB1066 B06-213555243Deutsche Forschungsgemeinschaft (German Research Foundation) SFB1450 C06-431460824Deutsche Forschungsgemeinschaft (German Research Foundation) SFB/TR156 start-up grantDeutsche Forschungsgemeinschaft (German Research Foundation) TR156 A04/C05-246807620Deutsche Forschungsgemeinschaft (German Research Foundation) TR156 C06-246807620Deutsche Krebshilfe (German Cancer Aid) Research Grant
6 · The paper itself

Abstract

Radiotherapy remains a mainstay of cancer treatment. However, radiotherapy can also elicit acute and chronic adverse effects, including dermal inflammation and skin fibrosis. A comprehensive understanding of the underlying fibrotic processes remains elusive, and currently, no established treatment options exist. Canonical Wnt signaling has emerged as a significant player in fibrotic conditions. The Dickkopf (DKK) protein family comprises key modulators of Wnt signaling. To define the function of DKK3 in radiation-induced skin damage, we combined complementary in vivo and in vitro approaches, including a 3D human skin model, mice with cell-type-specific Dkk3 deletions, and irradiated human skin specimens. Our study revealed the pivotal role of DKK3 in regulating the response of the skin to radiation, with diminished DKK3 significantly mitigating radiation-induced skin damage. We found that radiation increases DKK3 expression in basal keratinocytes, leading to elevated ROS levels, TGF-β-mediated Wnt activation, epidermal hyperplasia, and subsequent skin fibrosis. Increased keratinocyte expression of DKK3 also drives macrophage polarization toward a CD163

Indexed as

Adaptor Proteins, Signal TransducingIntercellular Signaling Peptides and ProteinsKeratinocytesRadiodermatitisWnt Signaling PathwayAnimalsChemokinesFibrosisHumansHyperplasiaMiceSkinAdaptor Proteins, Signal TransducingChemokinesDKK3 protein, humanDkk3 protein, mouseIntercellular Signaling Peptides and Proteins

Identifiers

PMID41629266
PMCPMC12864833

What OpenQuestion holds

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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.