title: Sphingosine-1-phosphate phosphatase 1 regulates keratinocyte differentiation and epidermal homeostasis.
abstract: Sphingosine 1-phosphate (S1P) is a bioactive lipid whose levels are tightly regulated by its synthesis and degradation. Intracellularly, S1P is dephosphorylated by the actions of two S1P-specific phosphatases, sphingosine-1-phosphate phosphatases 1 and 2. To identify the physiological functions of S1P phosphatase 1, we have studied mice with its gene, Sgpp1, deleted. Sgpp1(-/-) mice appeared normal at birth, but during the 1st week of life they exhibited stunted growth and suffered desquamation, with most dying before weaning. Both Sgpp1(-/-) pups and surviving adults exhibited multiple epidermal abnormalities. Interestingly, the epidermal permeability barrier developed normally during embryogenesis in Sgpp1(-/-) mice. Keratinocytes isolated from the skin of Sgpp1(-/-) pups had increased intracellular S1P levels and displayed a gene expression profile that indicated overexpression of genes associated with keratinocyte differentiation. The results reveal S1P metabolism as a regulator of keratinocyte differentiation and epidermal homeostasis.
authors: Genetics of Development and Disease Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Maria L
authors: ML
authors: Allende
authors: Laura M
authors: LM
authors: Sipe
authors: Galina
authors: G
authors: Tuymetova
authors: Kelsey L
authors: KL
authors: Wilson-Henjum
authors: Weiping
authors: W
authors: Chen
authors: Richard L
authors: RL
authors: Proia
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D016000:Cluster Analysis; D004817:Epidermis / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006706:Homeostasis / Q000235:genetics; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D008246:Lysophospholipids / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D010744:Phosphoric Monoester Hydrolases / Q000172:deficiency / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism; D013997:Time Factors
chemical_list: D008246:Lysophospholipids; D008565:Membrane Proteins; C060506:sphingosine 1-phosphate; C401298:sphingosine-1-phosphate phosphatase; D010744:Phosphoric Monoester Hydrolases; D013110:Sphingosine
keywords: Epidermis; Keratinocytes; Metabolism; Sgpp1; Sphingolipid; Sphingosine-1-phosphate
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