Antagonistic effects of TGFbeta1 and BMP-6 on skin keratinocyte differentiation.

McDonnell MA, Law BK, Serra R, Moses HL
Exp Cell Res. 2001 263 (2): 265-73

PMID: 11161725 · DOI:10.1006/excr.2000.5117

Several members of the transforming growth factor beta (TGFbeta) superfamily are expressed in the developing murine epidermis. Among these are TGFbeta1, which is found in the basal layer, and bone morphogenetic protein (BMP)-6, located in the suprabasal layers. Although the role of TGFbeta 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, TGFbeta1 antagonizes keratinocyte differentiation blocking the upregulation of keratin markers by BMP-6. 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.

Copyright 2001 Academic Press.

MeSH Terms (21)

Adenoviridae Animals Biomarkers Blotting, Northern Blotting, Western Bone Morphogenetic Protein 6 Bone Morphogenetic Proteins Cell Differentiation DNA-Binding Proteins Female Keratinocytes Keratins Male MAP Kinase Kinase 4 Mice Mitogen-Activated Protein Kinase Kinases Phosphorylation Signal Transduction Transduction, Genetic Transforming Growth Factor beta Transforming Growth Factor beta1

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