Figure 2.

Proposed role for sphingomyelinase phosphodiesterase acid-like 3b (SMPDL3b) in radiation and diabetic kidney disease-induced podocytopathy. Radiation causes the downregulation of SMPDL3B, altering the sphingolipid metabolism. Ceramide levels increase while sphingosine and sphingosine 1 phosphate levels decrease. This leads to the dephosphorylation of ezrin and subsequent actin remodeling and resorption of filopodia. However, in diabetic kidney disease (DKD) SMPDL3B levels are elevated and bind to increased circulating soluble urokinase plasminogen activator receptor (suPAR), thus inhibiting the activation of αVβ3, but enabling RhoA activation and increasing podocyte apoptosis.