Antagonistic effects of TGFβ1 and BMP-6 on skin keratinocyte differentiation

Several members of the transforming growth factor beta (TGF beta) superfamily are expressed in the developing murine epidermis, Among these are TGF beta1, which is found in the basal layer, and bone morphogenetic protein (BMP)-6, located in the suprabasal layers. Although the role of TGF beta in cell growth has been studied extensively, little is known about the effects of these factors on keratinocyte differentiation. This study demonstrates that BMP-6 acts to positively regulate the differentiation of primary skin keratinocytes grown in culture. In contrast, TGF beta1 antagonizes keratinocyte differentiation blocking the upregulation of keratin markers by BMP-g, We show that the effects of BMP-6 on expression of keratin 1 (K1), a marker of differentiation, requires signaling through the Smad pathway. In addition, regulation of K1 levels by BMP-6 is modulated by the SEK signaling pathway. This suggests that regulation of keratinocyte differentiation by BMP-6 involves multiple signaling systems, (C) 2001 Academic Press.