The effect of hypoxia on lipid phosphate receptor and sphingosine kinase expression and mitogen-activated protein kinase signaling in human pulmonary smooth muscle cells.

Both acute and chronic hypoxia had no effect on S1P(1), S1P(3) or LPA(1) receptor transcript expression in human pulmonary smooth muscle cells. However, acute hypoxia increased sphingosine kinase SK1/2 and LPP1 mRNA transcript levels, while chronic hypoxia increased SK1 mRNA transcript alone. Acute hypoxia had no effect on S1P-, PDGF- or phorbol ester (PMA)-stimulated activation of ERK-1/2, but increased the ability of S1P to activate p38 MAPK. Chronic hypoxia increased the ability of S1P to stimulate the phosphorylation of ERK-1/2. Therefore, we have demonstrated for the first time that hypoxia can lead to marked changes in the expression of genes involved in S1P production and may modify post S1P receptor signal transduction pathways.