Elucidation of pathogenic mechanisms for Fabry disease by transcriptome analysis (690.10)

Fabry disease is an X-linked inborn error of glycosphingolipid metabolism associated with deficient alpha-galactosidase A activity. The major clinical feature of Fabry disease, such as fibrosis in cardiomyopathy and renal failure has been observed with abnormal accumulation of globotriaosylceramide (Gb3) in biological fluids, vascular endothelium, heart and kidney. In addition to Gb3, increased concentration of deacylated Gb3 (lyso-Gb3) in the plasma of symptomatic patients also has been suggested as a causative molecular event. However, the correlation between fibrogenesis and elevated levels of these sphingolipids is poorly understood. To elucidate the genetic mechanisms involved in renal fibrosis in fabry disease, we analyzed the changes of global gene expression before and after Gb3 or lyso-Gb3 treatment on two types of kidney cell lines, human proximal renal tubular epithelial cells (HK-2) and mouse renal glomerular mesangial cells (SV40MES13), using microarray. The results showed that Gb3 and lyso-G...