FIGURE 10.

Schematic representation of signaling pathways involved in S1P-induced COX-2/PGE₂ expression in HCFs. Binding of S1P to G_q- or PTX-sensitive G_i protein-coupled S1PR1/3 results in PKCα-dependent phosphorylation of MAPKs (i.e., p42/p44 MAPK, p38 MAPK, and JNK1/2) leading to activation of NF-κB. The COX-2 transcription is dependently regulated by MAPK-mediated NF-κB cascades. These signaling pathways contribute to d activation of NF-κB required for COX-2 expression and PGE₂ generation in HCFs.