Growth and differentiation regulate CD44 expression on human keratinocytes |
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Authors: | Jing Zhou John G Haggerty Leonard M Milstone |
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Institution: | (1) Department of Dermatology, Yale University School of Medicine and Veterans Affairs Medical Center, 06510 New Haven, Connecticut |
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Abstract: | Summary Several members of the CD44 family of hyaluronan receptors are expressed on keratinocytes. To identify factors that might
be important in regulating CD44 expression, we studied CD44 expression on keratinocytes growing in vitro under a variety of
conditions and on cells isolated directly from epidermis. Using Western immunoblots and metabolic labeling, we showed that
the pattern of CD44 proteins expressed by keratinocytes was strongly influenced by growth and differentiation. Many protein
forms of CD44 are expressed on proliferating keratinocytes in preconfluent cultures, whereas only a few forms are expressed
on differentiated cells and in confluent cultures. In preconfluent monolayers, at least four splice variants were identified,
including epican, CD44H, CD44E, and a 180-kDa variant. In differentiated cells or in confluent cultures, by contrast, only
epican and the 180-kDa protein variant were found. Synthesis of all variants is strongly downregulated when keratinocytes
become confluent or when they differentiate. Epican is the predominant form of CD44 on keratinocytes under all conditions
and is expressed as a heparan, chondroitin, or keratan sulfate proteoglycan. Preconfluent basal keratinocytes, but not confluent
or differentiated keratinocytes, also express chondroitin sulfate proteoglycan forms of CD44E and of the 180-kDa core protein.
The modal size of the epican expressed on differentiated keratinocytes is smaller than the size of the epican expressed on
basal keratinocytes. Thus, cell confluence and differentiation regulate several aspects of CD44 expression on keratinocytes,
suggesting nuances in function for the different protein forms. |
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Keywords: | epidermis proteoglycans hyaluronan epican |
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