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ResearchIn-Press PreviewCell biologyDermatology Open Access | 10.1172/jci.insight.197838

Multi-omics analysis reveals dermokine as a regulator of keratinocyte differentiation and adhesion

Vahap Canbay,1 Till Wüstemann,2 Weihua Tian,1 Tobias A. Beyer,3 Camilla Reiter Elbæk,1 Michael Stumpe,4 Gaetana Restivo,5 Chatpakorn Christiansen,1 Anabel Migenda Herranz,3 Susanne Mailand,3 Jürg Hafner,5 Rune Busk Damgaard,1 Steffen Goletz,1 Jörn Dengjel,4 Ulrich auf dem Keller,1 and Chiara Francavilla1

1Department for Bioengineering and Biomedicine, Technical University of Denmark, Copenhagen, Denmark

2Department of Biology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

3Cytosurge AG, Zurich, Switzerland

4Department of Biology, University of Fribourg, Fribourg, Switzerland

5Department of Dermatology, University Hospital Zurich, Zurich, Switzerland

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1Department for Bioengineering and Biomedicine, Technical University of Denmark, Copenhagen, Denmark

2Department of Biology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

3Cytosurge AG, Zurich, Switzerland

4Department of Biology, University of Fribourg, Fribourg, Switzerland

5Department of Dermatology, University Hospital Zurich, Zurich, Switzerland

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1Department for Bioengineering and Biomedicine, Technical University of Denmark, Copenhagen, Denmark

2Department of Biology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

3Cytosurge AG, Zurich, Switzerland

4Department of Biology, University of Fribourg, Fribourg, Switzerland

5Department of Dermatology, University Hospital Zurich, Zurich, Switzerland

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1Department for Bioengineering and Biomedicine, Technical University of Denmark, Copenhagen, Denmark

2Department of Biology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

3Cytosurge AG, Zurich, Switzerland

4Department of Biology, University of Fribourg, Fribourg, Switzerland

5Department of Dermatology, University Hospital Zurich, Zurich, Switzerland

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1Department for Bioengineering and Biomedicine, Technical University of Denmark, Copenhagen, Denmark

2Department of Biology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

3Cytosurge AG, Zurich, Switzerland

4Department of Biology, University of Fribourg, Fribourg, Switzerland

5Department of Dermatology, University Hospital Zurich, Zurich, Switzerland

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1Department for Bioengineering and Biomedicine, Technical University of Denmark, Copenhagen, Denmark

2Department of Biology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

3Cytosurge AG, Zurich, Switzerland

4Department of Biology, University of Fribourg, Fribourg, Switzerland

5Department of Dermatology, University Hospital Zurich, Zurich, Switzerland

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1Department for Bioengineering and Biomedicine, Technical University of Denmark, Copenhagen, Denmark

2Department of Biology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

3Cytosurge AG, Zurich, Switzerland

4Department of Biology, University of Fribourg, Fribourg, Switzerland

5Department of Dermatology, University Hospital Zurich, Zurich, Switzerland

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1Department for Bioengineering and Biomedicine, Technical University of Denmark, Copenhagen, Denmark

2Department of Biology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

3Cytosurge AG, Zurich, Switzerland

4Department of Biology, University of Fribourg, Fribourg, Switzerland

5Department of Dermatology, University Hospital Zurich, Zurich, Switzerland

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1Department for Bioengineering and Biomedicine, Technical University of Denmark, Copenhagen, Denmark

2Department of Biology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

3Cytosurge AG, Zurich, Switzerland

4Department of Biology, University of Fribourg, Fribourg, Switzerland

5Department of Dermatology, University Hospital Zurich, Zurich, Switzerland

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1Department for Bioengineering and Biomedicine, Technical University of Denmark, Copenhagen, Denmark

2Department of Biology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

3Cytosurge AG, Zurich, Switzerland

4Department of Biology, University of Fribourg, Fribourg, Switzerland

5Department of Dermatology, University Hospital Zurich, Zurich, Switzerland

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1Department for Bioengineering and Biomedicine, Technical University of Denmark, Copenhagen, Denmark

2Department of Biology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

3Cytosurge AG, Zurich, Switzerland

4Department of Biology, University of Fribourg, Fribourg, Switzerland

5Department of Dermatology, University Hospital Zurich, Zurich, Switzerland

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1Department for Bioengineering and Biomedicine, Technical University of Denmark, Copenhagen, Denmark

2Department of Biology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

3Cytosurge AG, Zurich, Switzerland

4Department of Biology, University of Fribourg, Fribourg, Switzerland

5Department of Dermatology, University Hospital Zurich, Zurich, Switzerland

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1Department for Bioengineering and Biomedicine, Technical University of Denmark, Copenhagen, Denmark

2Department of Biology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

3Cytosurge AG, Zurich, Switzerland

4Department of Biology, University of Fribourg, Fribourg, Switzerland

5Department of Dermatology, University Hospital Zurich, Zurich, Switzerland

Find articles by Goletz, S. in: PubMed | Google Scholar

1Department for Bioengineering and Biomedicine, Technical University of Denmark, Copenhagen, Denmark

2Department of Biology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

3Cytosurge AG, Zurich, Switzerland

4Department of Biology, University of Fribourg, Fribourg, Switzerland

5Department of Dermatology, University Hospital Zurich, Zurich, Switzerland

Find articles by Dengjel, J. in: PubMed | Google Scholar

1Department for Bioengineering and Biomedicine, Technical University of Denmark, Copenhagen, Denmark

2Department of Biology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

3Cytosurge AG, Zurich, Switzerland

4Department of Biology, University of Fribourg, Fribourg, Switzerland

5Department of Dermatology, University Hospital Zurich, Zurich, Switzerland

Find articles by auf dem Keller, U. in: PubMed | Google Scholar

1Department for Bioengineering and Biomedicine, Technical University of Denmark, Copenhagen, Denmark

2Department of Biology, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland

3Cytosurge AG, Zurich, Switzerland

4Department of Biology, University of Fribourg, Fribourg, Switzerland

5Department of Dermatology, University Hospital Zurich, Zurich, Switzerland

Find articles by Francavilla, C. in: PubMed | Google Scholar

Published April 23, 2026 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.197838.
Copyright © 2026, Canbay et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published April 23, 2026 - Version history
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Abstract

Impaired adhesion and differentiation of keratinocytes is a hallmark of several skin diseases, but only some of the factors that regulate these processes have been identified. Here, we studied the role of isoform-rich dermokine – a wound- and tumor-regulated protein – in keratinocytes using a combination of multi-omics and functional approaches. CRISPR/Cas9-induced knockout of dermokine isoforms in human keratinocytes inhibited differentiation of these cells in three-dimensional organotypic skin cultures, which was confirmed by quantitative proteomics. In two-dimensional monocultures, dermokine deficiency affected the proteome and phosphoproteome as revealed by mass spectrometry. We found reduced abundance of differentiation-specific proteins and increased phosphorylation of cell adhesion protein p120 (catenin-δ1). The adhesive strength of dermokine knockout keratinocytes was impaired, which was rescued by p120 knock-down or ROCK inhibition. Finally, we verified the correlation between decreased dermokine expression and increased p120 phosphorylation in human non-healing wounds. These results identify dermokine as regulator of keratinocyte adhesion and differentiation, involving at least in part its effect on p120 phosphorylation and ROCK. Our data point to a function of dermokine in the pathogenesis of chronic wounds.

Graphical Abstract
graphical abstract
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  • Version 1 (April 23, 2026): In-Press Preview
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