Lyso-Gb3 Increases αvβ3 Integrin Gene Expression in Cultured Human Podocytes in Fabry Nephropathy.

Background: Podocyturia in Fabry nephropathy leads to glomerulosclerosis and kidney disease progression. Integrins are involved in podocyte attachment to the glomerular basement membrane. We hypothesized that in Fabry nephropathy, lyso-Gb3 could modulate αvβ3 expression in podocytes. Together with UPAR, the αvβ3 integrin is a key mechanism involved in podocyte detachment and podocyturia.

Methods: In cultured human podocytes stimulated with lyso-Gb3, the mRNA expression of the and genes encoding integrins αv and β3, respectively, was analyzed by RT-qPCR.

Results: In cultured human podocytes, lyso-Gb3 at concentrations encountered in the serum of Fabry patients increased and mRNA levels within 3 to 6 h. This pattern of gene expression is similar to that previously observed for gene expression but is in contrast to the delayed (24 h) upregulation of other markers of podocyte stress and mediators of injury, such as CD80, TGFβ1, CD74, Notch1, and HES.

Conclusions: Human podocyte stress in response to glycolipid overload in Fabry nephropathy, exemplified by lyso-Gb3, is characterized by an early increase in the expression of components of the αvβ3/UPAR system, which contrasts with the delayed rise in the expression of other mediators of podocyte injury. This suggests that the αvβ3/UPAR system may be a therapeutic target in Fabry nephropathy.