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The G 60 S C x43 mutant enhances keratinocyte proliferation and differentiation
Author(s) -
Churko Jared M.,
Kelly John J.,
MacDonald Andrew,
Lee Jack,
Sampson Jacinda,
Bai Donglin,
Laird Dale W.
Publication year - 2012
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.1600-0625.2012.01532.x
Subject(s) - involucrin , keratinocyte , loricrin , mutant , epidermis (zoology) , microbiology and biotechnology , wound healing , biology , cellular differentiation , chemistry , cell culture , immunology , anatomy , biochemistry , genetics , gene
Transient knock‐down of the gap junction protein C x43 by antisense and si RNA , or gap junction block with mimetic peptides, have been shown to enhance epidermal wound healing. However, patients with oculodentodigital dysplasia ( ODDD ) express mutant C x43 that leads to a chronic reduction in gap junctional intercellular communication. To determine whether mutant C x43 in keratinocytes would impact upon the wound healing process, we localized C x43 in human and mouse skin tissue expressing mutant C x43 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 G 60 S mutant or in keratinocytes obtained from mutant mice, C x43 was frequently found within intracellular compartments and rarely localized to punctate sites of cell–cell apposition. Primary keratinocytes derived from G 60 S mutant mice proliferated faster but migrated similarly to keratinocytes derived from wild‐type control mice. Keratinocytes derived from mutant mice expressed abundant C x43 and higher levels of involucrin and loricrin under low calcium conditions. However, after calcium‐induced differentiation, similar levels of C x43, involucrin and loricrin were observed. Thus, we conclude that during wound healing, mutant C x43 may enhance keratinocyte proliferation and promote early differentiation of keratinocytes.