The hSkn-1a POU transcription factor enhances epidermal stratification by promoting keratinocyte proliferation

Jeffrey Hildesheim, Ulrich Kühn, Carole L. Yee, Ruth A. Foster, Kim B. Yancey, Jonathan C. Vogel

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Skn-1a is a POU transcription factor that is primarily expressed in the epidermis and is known to modulate the expression of several genes associated with keratinocyte differentiation. However, the formation of a stratified epidermis requires a carefully controlled balance between keratinocyte proliferation and differentiation, and a role for Skn-1a in this process has not been previously demonstrated. Here, our results show, surprisingly, that human Skn-1a contributes to epidermal stratification by primarily promoting keratinocyte proliferation and secondarily by enhancing the subsequent keratinocyte differentiation. In organotypic raft cultures of both primary human keratinocytes and immortalized HaCaT keratinocytes, human Skn-1a expression is associated with increased keratinocyte proliferation and re-epithelialization of the dermal substrates, resulting in increased numbers of keratinocytes available for the differentiation process. In these same raft cultures, human Skn-1a expression enhances the phenotypic changes of keratinocyte differentiation and the upregulated expression of keratinocyte differentiation genes. Conversely, expression of a dominant negative human Skn-1a transcription factor lacking the C-terminal transactivation domain blocks keratinocytes from proliferating and stratifying. Keratinocyte stratification is dependent on a precise balance between keratinocyte proliferation and differentiation, and our results suggest that human Skn-1a has an important role in maintaining epidermal homeostasis by promoting keratinocyte proliferation.

Original languageEnglish (US)
Pages (from-to)1913-1923
Number of pages11
JournalJournal of cell science
Volume114
Issue number10
StatePublished - Jun 23 2001

Keywords

  • Differentiation
  • HaCaT cells
  • Human keratinocyte
  • Proliferation
  • Raft cultures

ASJC Scopus subject areas

  • Cell Biology

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    Hildesheim, J., Kühn, U., Yee, C. L., Foster, R. A., Yancey, K. B., & Vogel, J. C. (2001). The hSkn-1a POU transcription factor enhances epidermal stratification by promoting keratinocyte proliferation. Journal of cell science, 114(10), 1913-1923.