A pentapeptide that inhibits proliferation of mouse epidermal keratinocytes in vivo and in vitro has been purified from mouse skin extracts. In the present study the effect of a synthetic analog of the epidermal pentapeptide on proliferation and differentiation of cultured human epidermal keratinocytes was investigated. In young, rapidly growing primary cultures the pentapeptide caused a dramatic decrease in mitotic activity and also induced pronounced changes in the balance between kinetically defined subpopulations of proliferating cells. A dipeptide derived from the pentapeptide was found to be at least as potent. A serine derivative of a hemoregulatory peptide also seemed to be active. When tested in epidermal cultures regenerating after removal of the suprabasal cell layers, both the pentapeptide and the dipeptide were shown to cause a delay in the proliferative response. Both peptides were also able to stimulate early (increase in cell size) and late (cornified envelope formation) events in the differentiation pathway of the keratinocyte. The apparent stimulatory effect on differentiation was most clearly seen in regenerating cultures, whereas the effect on primary cultures varied with the experimental set-up. It is suggested that homologous epidermal peptide(s) may play a major role in the regulation of human epidermal homeostasis.
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