Altered expression of dermokine in skin disorders

J Eur Acad Dermatol Venereol. 2013 Jul;27(7):867-75. doi: 10.1111/j.1468-3083.2012.04598.x. Epub 2012 May 31.

Abstract

Background: Although dermokine-β, a glycoprotein expressed in epithelial cells, does not have significant homology to other proteins, its carboxyl-terminal domain shares a high pI value with many cytokines, suggesting similar functions.

Objective: To better understand the biology of dermokine, we here determined its localization under pathological conditions and examined factors that regulate its expression.

Methods: We generated an anti-human dermokine-β/γ monoclonal antibody cross-reacting with the mouse protein. Using this antibody, immunohistological staining and Western blotting of dermokine-β/γ were performed with various tissue samples.

Results: Although human dermokine-β/γ was expressed in almost all granular layers, upper spinous layers of the skin were also stained with anti-dermokine-β/γ antibody in inflammatory skin disorders. Dermokine-β/γ was expressed in keratoacanthoma and a part of well-differentiated squamous cell carcinoma (SCC). However, dermokine-β/γ was not detected in poorly differentiated SCC or tumours derived from non-keratinocytes. In mice, dermokine-β/γ-expressed keratinocytes were increased in models of contact hypersensitivity, ultraviolet-irradiated skin injury and wound healing. Consistent with expanded distribution in inflammatory skin diseases, proinflammatory cytokines such as interleukin-1β, interleukin-12, and tumour necrosis factor-α augmented dermokine-β/γ expression in cultured human keratinocytes. In contrast, growth factors including epidermal growth factor, insulin-like growth factor-I, keratinocyte growth factor and transforming growth factor-α significantly reduced dermokine expression.

Conclusion: These results provide novel insights into the physiological and pathological significance of dermokine in the epidermis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Gene Expression Regulation
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Mice
  • Mice, Inbred C57BL
  • Proteins* / analysis
  • Proteins* / genetics
  • Skin / chemistry
  • Skin Diseases / genetics
  • Skin Diseases / metabolism*

Substances

  • DMKN protein, human
  • Intercellular Signaling Peptides and Proteins
  • Proteins