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Transforming growth factor-β (TGF-β) signaling plays a pivotal role in extracellular matrix deposition by stimulating collagen production and other extracellular matrix proteins and by inhibiting matrix degradation. The present study was undertaken to define the role of sphingosine kinase (SphK) in TGF-β signaling. TGF-β markedly up-regulated SphK1 mRNA and protein amounts and caused a prolonged increase in SphK activity in dermal fibroblasts. Concomitantly, TGF-β reduced sphingosine-1-phosphate phosphatase activity. Consistent with the changes in enzyme activity, corresponding changes in sphingolipid levels were observed such that sphingosine 1-phosphate (S1P) was increased (∼2-fold), whereas sphingosine and ceramide were reduced after 24 h of TGF-β treatment. Given the relatively early induction of SphK gene expression in response to TGF-β, we examined whether SphK1 may be involved in …