Connexin levels regulate keratinocyte differentiation in the epidermis.

Connexin levels regulate keratinocyte differentiation in the epidermis. Research Abstract Details 

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Connexin levels regulate keratinocyte differentiation in the epidermis. Abstract Text:

Langlois,Amy C Maher,Janet L Manias,Qing Shao,Gerald M Kidder,Dale W Laird, Langlois,Amy C Maher,Janet L Manias,Qing Shao,Gerald M Kidder,Dale W Laird,

To understand the role of connexin43 (Cx43) in epidermal differentiation, we reduced Cx43 levels by RNA-mediated interference knockdown and impaired its functional status by overexpressing loss-of-function Cx43 mutants associated with the human disease oculodentodigital dysplasia (ODDD) in rat epidermal keratinocytes. When Cx43 expression was knocked down by 50-75%, there was a coordinate 55-65% reduction in Cx26 level, gap junction-based dye coupling was reduced by 60%, and transepithelial resistance decreased. Importantly, the overall growth and differentiation of Cx43 knockdown organotypic epidermis was severely impaired as revealed by alterations in the levels of the differentiation markers loricrin and involucrin and by reductions in vital and cornified layer thicknesses. Conversely, although the expression of Cx43 mutants reduced the coupling status of rat epidermal keratinocytes by approximately 80% without altering the levels of endogenous Cx43 or Cx26, their ability to differentiate was not altered. In addition, we used a mouse model of ODDD and found that newborn mice harboring the loss-of-function Cx43(G60S) mutant had slightly reduced Cx43 levels, whereas Cx26 levels, epidermis differentiation, and barrier function remained unaltered. This properly differentiated epidermis was maintained even when Cx43 and Cx26 levels decreased by more than 70% in 3-week-old mutant mice. Our studies indicate that Cx43 and Cx26 collectively co-regulate epidermal differentiation from basal keratinocytes but play a more minimal role in the maintenance of established epidermis. Altogether, these studies provide an explanation as to why the vast majority of ODDD patients, where Cx43 function is highly compromised, do not suffer from skin disease.

Connexin levels regulate keratinocyte differentiation in the epidermis. Publishing Authors By Initials

S Langlois,AC Maher,JL Manias,Q Shao,GM Kidder,DW Laird,S Langlois,AC Maher,JL Manias,Q Shao,GM Kidder,DW Laird,

For similar integumentary system: skin research abstracts see: integumentary system: skin research

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Connexin levels regulate keratinocyte differentiation in the epidermis. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of biological chemistry

VOLUME: 282

Page Numbers: 30171-80

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 10

MONTH: 08

YEAR: 2007

Connexin levels regulate keratinocyte differentiation in the epidermis. Information

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LANGUAGE: eng

NlmUniqueID: 2985121

Connexin levels regulate keratinocyte differentiation in the epidermis. Keywords Mesh Terms:

KEYWORDS: Skin

MESH TERMS: metabolism

Chemical & Substance for Abstract: Connexin levels regulate keratinocyte differentiation in the epidermis. Information

Substance Name: connexin 26

Registry Number: 127120-53-0

Grant and Affiliation Information for Connexin levels regulate keratinocyte differentiation in the epidermis.

AFFILIATION: Department of Anatomy and Cell Biology, The University of Western Ontario, London, Ontario, N6A 5C1, Canada.

Country: United States

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MEDLINETA: J Biol Chem

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