title: Overexpression of constitutively active BMP-receptor-IB in mouse skin causes an ichthyosis-vulgaris-like disease.
abstract: The skin is the outer layer of protection against the environment. The development and formation of the skin is regulated by several genetic cascades including the bone morphogenetic protein (BMP) signaling pathway, which has been suggested to play an important role during embryonic organ development. Several skin defects and diseases are caused by genetic mutations or disorders. Ichthyosis is a common genetic skin disorder characterized by dry scaly skin. Loss-of-function mutations in the filaggrin (FLG) gene have been identified as the cause of the ichthyosis vulgaris (IV) phenotype; however, the direct regulation of filaggrin expression in vivo is unknown. We present evidence that BMP signaling regulates filaggrin expression in the epidermis. Mice expressing a constitutively active form of BMP-receptor-IB in the developing epidermis exhibit a phenotype resembling IV in humans, including dry flaky skin, compact hyperkeratosis, and an attenuated granular layer associated with a significantly downregulated expression of filaggrin. Regulation of filaggrin expression by BMP signaling has been further confirmed by the application of exogenous BMP2 in skin explants and by a transgenic model overexpressing Noggin in the epidermis. Our results demonstrate that aberrant BMP signaling in the epidermis causes overproliferation and hyperkeratinization, leading to an IV-like skin disease.
authors.affiliation: Section of Oral Biology, The Ohio State University College of Dentistry, Columbus, OH 43210, USA.
authors.forename: Xueyan
authors.initials: X
authors.lastname: Yu
authors.forename: Ramón A
authors.initials: RA
authors.lastname: Espinoza-Lewis
authors.forename: Cheng
authors.initials: C
authors.lastname: Sun
authors.forename: Lisong
authors.initials: L
authors.lastname: Lin
authors.forename: Fenglei
authors.initials: F
authors.lastname: He
authors.forename: Wei
authors.initials: W
authors.lastname: Xiong
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.forename: Alun
authors.initials: A
authors.lastname: Wang
authors.forename: Yiping
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics / Q000378:metabolism*; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics; D002454:Cell Differentiation; D049109:Cell Proliferation; D004817:Epidermis / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D000091344:Filaggrin Proteins; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D005838:Genotype; D016112:Ichthyosis Vulgaris / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007381:Intermediate Filament Proteins / Q000235:genetics; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D016133:Polymerase Chain Reaction; D015398:Signal Transduction; D000099176:Noggin Protein
chemical_list: D052005:Bone Morphogenetic Protein Receptors, Type I; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D000099176:Noggin Protein; C000717249:FLG protein, human