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]