Characterization of Human Dermal Fibroblasts in Fabry Disease.

Abstract

Fabry disease (FD) is a hereditary X-linked metabolic lysosomal storage disorder due to insufficient amounts or a complete lack of the lysosomal enzyme α-galactosidase A (α-GalA). The loss of α-GalA activity leads to an abnormal accumulation of globotriaosylcerami (Gb3) in lysosomes and other cellular components of different tissues and cell types, affecting the cell function. However, whether these biochemical alterations also modify functional processes associated to the cell mitotic ability is still unknown. The goal of the present study was to characterize lineages of human dermal fibroblasts (HDFs) of FD patients and healthy controls focusing on Gb3 accumulation, expression of chloride channels that regulate proliferation, and proliferative activity. The biochemical and functional analyses indicate the existence of quantitative differences in some but not all the parameters of cytoskeletal organization, proliferation, and differentiation processes.