title: BMP signaling induces cell-type-specific changes in gene expression programs of human keratinocytes and fibroblasts.
abstract: BMP signaling has a crucial role in skin development and homeostasis, whereas molecular mechanisms underlying its involvement in regulating gene expression programs in keratinocytes and fibroblasts remain largely unknown. We show here that several BMP ligands, all BMP receptors, and BMP-associated Smad1/5/8 are expressed in human primary epidermal keratinocytes and dermal fibroblasts. Treatment of both cell types by BMP-4 resulted in the activation of the BMP-Smad, but not BMP-MAPK pathways. Global microarray analysis revealed that BMP-4 treatment induces distinct and cell type-specific changes in gene expression programs in keratinocytes and fibroblasts, which are far more complex than the effects of BMPs on cell proliferation/differentiation described earlier. Furthermore, our data suggest that the potential modulation of cell adhesion, extracellular matrix remodeling, motility, metabolism, signaling, and transcription by BMP-4 in keratinocytes and fibroblasts is likely to be achieved by the distinct and cell-type-specific sets of molecules. Thus, these data provide an important basis for delineating mechanisms that underlie the distinct effects of the BMP pathway on different cell populations in the skin, and will be helpful in further establishing molecular signaling networks regulating skin homeostasis in health and disease.
authors.affiliation: Centre for Skin Sciences, School of Life Sciences, University of Bradford, Bradford, UK.
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Fessing
authors.forename: Ruzanna
authors.initials: R
authors.lastname: Atoyan
authors.forename: Ben
authors.initials: B
authors.lastname: Shander
authors.forename: Andrei N
authors.initials: AN
authors.lastname: Mardaryev
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Botchkarev
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Poterlowicz
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Peng
authors.forename: Tatiana
authors.initials: T
authors.lastname: Efimova
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Botchkarev
mesh_terms: D028341:Activins / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002448:Cell Adhesion; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D015603:Keratinocytes / Q000166:cytology*; D008024:Ligands; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D008024:Ligands; D016212:Transforming Growth Factor beta; D028341:Activins