Table 1: Organ Fibrosis in which S1P, dhS1P, Ceramide and/or their Synthetic Enzymes have been Implicated

Affected Organ Sphingolipid/ Enzyme Implicated Receptor(s) Implicated Pro- or Anti-Fibrotic Role Proposed Mechanism(s) References

Lung fibrosis S1P S1P1 Anti-fibrotic Attenuation of vascular leak and intra-alveolar coagulation [13]
Acid sphingomyelinase (ASM) ? Pro-fibrotic Promotion of cellular apoptosis and fibroblast collagen synthesis [76]

Skin fibrosis/ Scleroderma S1P S1P1,2 Pro-fibrotic Cross-activation of fibroblast TGF-β/ Smad signaling; myofibroblast differentiation [78-81]
dhS1P S1P1,2 Anti-fibrotic Inhibition of fibroblast TGF-β/Smad signaling through PTEN upregulation [14, 81]

Liver fibrosis S1P S1P2,3 Pro-fibrotic Hepatic stellate cell accumulation and activation; homing of bone marrow-derived cells to the injured liver [15, 84-88]
Ceramide/Acid sphingomyelinase (ASM) ? Pro-fibrotic Inhibition of fibroblast TGF-β/Smad signaling through PTEN upregulation [89-92]

Cardiac fibrosis S1P S1P2,3 Pro-fibrotic Promotion of hepatocyte apoptosis; hepatic stellate cell proliferation and activation [16, 75]

Retinal fibrosis S1P ? Pro-fibrotic Promotion of retinal pigmented epithelial cell proliferation, myofibroblast differentiation, and collagen synthesis [17, 93]