Transforming growth factor-beta and Vascular Endothelial Growth Factor Expressions in the Kidney of Fabry Mouse

Fabry disease is a lysosomal storage disorder caused by deficiency of α-galactosidase A, which results in deposition of globotriaosylceramide (Gb3) in lysosomes. Patients develop painful neuropathy, vascular occlusions that progressively lead to cardiovascular, cerebrovascular, and renal dysfunction and early death. Since the level of Gb3 and clinical manifestations of Fabry disease have not been correlated, we investigated altered gene expressions in Fabry mouse kidney. Microarray analysis revealed that renal Tsps (Thrombospondins) were significantly up-regulated in Fabry mouse kidney. Tsp-1 and Tsp-2 act as inhibitors of angiogenesis that is an extracellular matrix protein involved in cell adhesion, proliferation and survival. Tsp-1 suppresses tumor growth through transforming growth factor-β (TGF-β) activation. Fibroblast growth factor-2 (FGF-2) induces vascular endothelial growth factor (VEGF) expression. Up-regulation of Tsp-1, VEGF, TGF-β1 and FGF-2 are associated to vascular and renal pathology in ...