The G60S Cx43 mutant enhances keratinocyte proliferation and differentiation

Jared M. Churko, John J. Kelly, Andrew Macdonald, Jack Lee, Jacinda Sampson, Donglin Bai, Dale W. Laird

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Transient knock-down of the gap junction protein Cx43 by antisense and siRNA, or gap junction block with mimetic peptides, have been shown to enhance epidermal wound healing. However, patients with oculodentodigital dysplasia (ODDD) express mutant Cx43 that leads to a chronic reduction in gap junctional intercellular communication. To determine whether mutant Cx43 in keratinocytes would impact upon the wound healing process, we localized Cx43 in human and mouse skin tissue expressing mutant Cx43 and assessed the ability of primary keratinocytes derived from a mouse model of ODDD to proliferate, migrate and differentiate. In the epidermis from an ODDD patient and in the epidermis of mice expressing the G60S mutant or in keratinocytes obtained from mutant mice, Cx43 was frequently found within intracellular compartments and rarely localized to punctate sites of cell-cell apposition. Primary keratinocytes derived from G60S mutant mice proliferated faster but migrated similarly to keratinocytes derived from wild-type control mice. Keratinocytes derived from mutant mice expressed abundant Cx43 and higher levels of involucrin and loricrin under low calcium conditions. However, after calcium-induced differentiation, similar levels of Cx43, involucrin and loricrin were observed. Thus, we conclude that during wound healing, mutant Cx43 may enhance keratinocyte proliferation and promote early differentiation of keratinocytes.

Original languageEnglish (US)
Pages (from-to)612-618
Number of pages7
JournalExperimental Dermatology
Volume21
Issue number8
DOIs
StatePublished - Aug 1 2012
Externally publishedYes

Keywords

  • Cx43
  • G60S
  • Keratinocytes
  • Oculodentodigital dysplasia
  • Proliferation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

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