Selective suppression of CD44 in keratinocytes of mice bearing an antisense CD44 transgene driven by a tissue-specific promoter disrupts hyaluronate metabolism in the skin and impairs keratinocyte proliferation

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Version: Final published version
Serval ID
serval:BIB_89A54A57EAC1
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Selective suppression of CD44 in keratinocytes of mice bearing an antisense CD44 transgene driven by a tissue-specific promoter disrupts hyaluronate metabolism in the skin and impairs keratinocyte proliferation
Journal
Genes and Development
Author(s)
Kaya  G., Rodriguez  I., Jorcano  J. L., Vassalli  P., Stamenkovic  I.
ISSN
0890-9369 (Print)
Publication state
Published
Issued date
1997
Volume
11
Number
8
Pages
996-1007
Language
english
Notes
PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S
Abstract
CD44 is a broadly distributed polymorphic glycoprotein that serves as the principal cell-surface receptor for hyaluronate. Although CD44-mediated cell interaction with hyaluronate has been implicated in a variety of physiologic events, including cell-cell and cell-substrate adhesion, cell migration, proliferation, and activation, as well as hyaluronate uptake and degradation, the biologic role of CD44 in vivo in various tissues remains to be determined. In the present work we have developed transgenic mice that express an antisense CD44 cDNA driven by the keratin-5 promoter. These mice lack detectable CD44 expression in skin keratinocytes and corneal epithelium and display abnormal hyaluronate accumulation in the superficial dermis and corneal stroma, distinct morphologic alterations of basal keratinocytes and cornea, and defective keratinocyte proliferation in response to mitogen and growth factors. These alterations are reflected by a decrease in skin elasticity, impaired local inflammatory response and tissue repair, delayed hair regrowth, and failure of the epidermis to undergo hyperplasia in response to carcinogen. Our observations indicate that two major functions of CD44 in skin are the regulation of keratinocyte proliferation in response to extracellular stimuli and the maintenance of local hyaluronate homeostasis
Keywords
9,10-Dimethyl-1,2-benzanthracene/pharmacology/Animals/Antigens,CD44/genetics/physiology/Carcinogens/Cattle/Cell Division/Cells,Cultured/Cornea/metabolism/DNA,Antisense/Elasticity/Epidermal Growth Factor/Epidermis/Pathology/ultrastructure/Epithelium/Fibroblast Growth Factor 2/Hyaluronic Acid/Keratinocytes/cytology/Keratins/Mice/Mice,Transgenic/Promoter Regions (Genetics)/Skin/drug effects/Tetradecanoylphorbol Acetate/Wound Healing
Pubmed
Web of science
Open Access
Yes
Create date
29/01/2008 18:35
Last modification date
20/08/2019 14:48
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