Figure 2

Schematic presentation of ceramide synthesis and its involvement in renal fibrosis. Ceramide is synthesized mainly by three processes: de novo synthesis, the salvage pathway, and sphingomyelin hydrolysis. Ceramide could cause renal fibrosis by enhancing ECM production, glomelular injury, proteinuria, and apoptosis. Triglycerides (TGs) and cholesterol (CHOL) accumulation in the kidney could also contribute to the development of renal fibrosis. At the same time, sphingosine kinase could contribute to renal fibrosis by enhancing cell migration and proliferation. The renoprotective activity of amitriptyline is due to its ability to inhibit the sphingomyelinase enzyme and thereby inhibit ceramide synthesis and to protect against renal fibrosis.