Sphingosine-1-phosphate Phosphatase 1 Regulates Keratinocyte Differentiation and Epidermal Homeostasis
Authors
Maria L. Allende, Laura M. Sipe, Galina Tuymetova, Kelsey L. Wilson-Henjum, Weiping Chen, and Richard L. Proia
Institution
NIH
Country
United States
Year
2013
Journal
JBC
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 phosphatase 1 and 2.
To identify the physiologic functions of S1P
phosphatase 1, we have studied mice with its
gene, Sgpp1, deleted. Sgpp1-/- mice appeared
normal at birth, but during the first week of life
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.