Multiomics analysis reveals dermokine as a regulator of keratinocyte differentiation and adhesion

Vahap Canbay1, Till Wüstemann2, Weihua Tian1

  • 1Department for Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark.

JCI Insight
|April 23, 2026
PubMed

Insights

Dermokine protein is crucial for skin cell adhesion and differentiation, impacting wound healing. Its deficiency impairs these processes by affecting cell adhesion protein p120 phosphorylation.

Area of Science:

  • Dermatology
  • Cell Biology
  • Molecular Biology

Background:

  • Keratinocyte adhesion and differentiation are vital for skin health and are impaired in various skin diseases.
  • The precise molecular regulators of these processes are not fully understood.

Purpose of the Study:

  • To investigate the role of dermokine, a wound- and tumor-regulated protein, in keratinocyte adhesion and differentiation.

Main Methods:

  • CRISPR/Cas9 gene editing to create dermokine isoform knockout keratinocytes.
  • Multi-omics approaches including quantitative proteomics and mass spectrometry (proteome and phosphoproteome analysis).
  • Three-dimensional organotypic skin cultures and two-dimensional monocultures.
  • Assessment of keratinocyte adhesive strength and rescue experiments.
  • Analysis of human non-healing wounds.

Main Results:

  • Dermokine knockout inhibited keratinocyte differentiation in 3D cultures, confirmed by proteomics.
  • Dermokine deficiency altered the proteome and phosphoproteome in 2D cultures, showing reduced differentiation markers and increased p120 (catenin-δ1) phosphorylation.
  • Impaired keratinocyte adhesion in dermokine knockout cells was rescued by p120 knockdown or ROCK inhibition.
  • Decreased dermokine expression correlated with increased p120 phosphorylation in human non-healing wounds.

Conclusions:

  • Dermokine regulates keratinocyte adhesion and differentiation, partly through its influence on p120 phosphorylation and ROCK signaling.
  • Dermokine plays a role in the pathogenesis of chronic wounds.

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