C/EBPalpha and C/EBPbeta are required for Sebocyte differentiation and stratified squamous differentiation in adult mouse skin

Autor: Keith E. Linder, Songyun Zhu, Robert C. Smart, Rakesh Ranjan, John S. House
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Keratinocytes
medicine.medical_specialty
Genotype
Squamous Differentiation
Cellular differentiation
Immunoblotting
Preputial gland
Cell Biology/Cell Growth and Division
Meibomian gland
lcsh:Medicine
Dermatology
Dermatology/Dermatologic Pathology
Biology
03 medical and health sciences
Basal (phylogenetics)
Mice
Sebaceous Glands
0302 clinical medicine
Internal medicine
medicine
CCAAT-Enhancer-Binding Protein-alpha
Animals
lcsh:Science
Melanocortin 5 receptor
Cell Biology/Gene Expression
030304 developmental biology
Cell Proliferation
Skin
0303 health sciences
Multidisciplinary
Epidermis (botany)
integumentary system
CCAAT-Enhancer-Binding Protein-beta
Cell Cycle
Homozygote
digestive
oral
and skin physiology
lcsh:R
Cell Differentiation
Epithelial Cells
Molecular biology
Immunohistochemistry
medicine.anatomical_structure
Endocrinology
Gene Expression Regulation
030220 oncology & carcinogenesis
lcsh:Q
biological phenomena
cell phenomena
and immunity
Keratinocyte
Research Article
Zdroj: PLoS ONE, Vol 5, Iss 3, p e9837 (2010)
PLoS ONE
ISSN: 1932-6203
Popis: C/EBPalpha and C/EBPbeta are bZIP transcription factors that are highly expressed in the interfollicular epidermis and sebaceous glands of skin and yet germ line deletion of either family member alone has only mild or no effect on keratinocyte biology and their role in sebocyte biology has never been examined. To address possible functional redundancies and reveal functional roles of C/EBPalpha and C/EBPbeta in postnatal skin, mouse models were developed in which either family member could be acutely ablated alone or together in the epidermis and sebaceous glands of adult mice. Acute removal of either C/EBPalpha or C/EBPbeta alone in adult mouse skin revealed modest to no discernable changes in epidermis or sebaceous glands. In contrast, co-ablation of C/EBPalpha and C/EBPbeta in postnatal epidermis resulted in disruption of stratified squamous differentiation characterized by hyperproliferation of basal and suprabasal keratinocytes and a defective basal to spinous keratinocyte transition involving an expanded basal compartment and a diminished and delayed spinous compartment. Acute co-ablation of C/EBPalpha and C/EBPbeta in sebaceous glands resulted in severe morphological defects, and sebocyte differentiation was blocked as determined by lack of sebum production and reduced expression of stearoyl-CoA desaturase (SCD3) and melanocortin 5 receptor (MC5R), two markers of terminal sebocyte differentiation. Specialized sebocytes of Meibomian glands and preputial glands were also affected. Our results indicate that in adult mouse skin, C/EBPalpha and C/EBPbeta are critically involved in regulating sebocyte differentiation and epidermal homeostasis involving the basal to spinous keratinocyte transition and basal cell cycle withdrawal.
Databáze: OpenAIRE
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