Growth and differentiation regulate CD-44 expression on human keratinocytes

Several members of the CD44 family of hyaluronan receptors are expressed on keratinocytes. To identify factors that might be important in regulating C D44 expression. we studied CD44 expression on keratinocytes growing in vitr o under a variety of conditions and on cells isolated directly from epiderm is. Using Western immunoblots and metabolic labeling, we showed that the pa ttern of CD44 proteins expressed by keratinocytes was strongly influenced b y growth and differentiation. Many protein forms of CD44 are expressed on p roliferating keratinocytes in preconfluent cultures, whereas only a few for ms are expressed on differentiated cells and in confluent cultures. In prec onfluent monolayers, at least four splice variants were identified, includi ng epican, CD44H, CD44E, and a 180-kDa variant. In differentiated cells or in confluent cultures, by contrast, only epican and thr 180-kDa protein var iant were found. Synthesis of all variants is strongly downregulated when k eratinocytes become confluent or when they differentiate. Epican is the pre dominant Form of CD44 on keratinocytes under all conditions and is expresse d as a heparan. chondroitin, or keratan sulfate proteoglycan. Preconfluent basal keratinocytes, but not confluent or differentiated keratinocytes, als o express chondroitin sulfate proteoglycan forms of CD44E and of the 180-kD a core protein. The modal size of the epican expressed on differentiated ke ratinocytes is smaller than the size of the epican expressed on basal kerat inocytes. Thus, cell confluence and differentiation regulate several aspect s of CD44 expression on keratinocytes, suggesting nuances in function for t he different protein forms.