Coexpression of keratins 13 and 16 in human keratinocytes indicates association between hyperproliferation-associated and retinoid-induced differentiation

In human skin, epidermal differentiation occurs in two ways: normal differe ntiation, characterized by keratin 10 expression, and alternative different iation, Alternative differentiation can be hyperproliferation-associated di fferentiation (expression of keratin 16) or the reinduction of an embryonic type of differentiation (expression of keratin 13), This embryonic type of differentiation is also seen following treatment with retinoids, In the pr esent study, the hypothesis that hyperproliferation-associated and retinoid -induced differentiation are separate processes was investigated, Two areas of normal skin were treated for 24 h with 0.1% all-trans-retinoic acid. Su bsequently, one of the areas was tape-stripped and treatment was continued for 48 h, Multiparameter flow cytometry permitted simultaneous measurement of two coexpressed differentiation markers (retinoid-induced and normal dif ferentiation or retinoid-induced and hyperproliferation-associated differen tiation) and the proliferation characteristics (cells in S/G(2)M phase). Co ncerning normal and retinoid-induced differentiation, the all-trans-retinoi c acid-induced expression of keratin 13 was only seen in tape-stripped reti noid-treated skin and exclusively together with that of keratin 10. The ass essment of hyperproliferation-associated and retinoid-induced differentiati on showed slight expression of keratin 13 without expression of keratin 16 in tape-stripped skin. Coexpression of keratins 16 and 13 was exclusively s een in tape-stripped retinoid-treated skin. The finding that keratin 13 exp ression following treatment with all-trans-retinoic acid occurred exclusive ly in hyperproliferative skin suggests that retinoid-induced and hyperproli feration-associated differentiation are coupled. Coexpression of keratins 1 3 and 16 provides direct experimental evidence for this association.