Fig. 9.

Overview of the molecular protective mechanisms of MLK against GM nephrotoxicity. Endocytosis of GM in proximal tubular epithelial cells is mediated through megalin (M)/cubilin (C) complex. The endocytic function of megalin receptor is regulated by ClC-5 through acidification of endosomes to facilitate dissociation between megalin and its ligand, then megalin recycles to the brush border membrane. MLK downregulates ClC-5 expression resulting in impaired endocytic function, megalin recycling, and so its expression on the cell membrane. Therefore, MLK could reduce GM uptake into renal cells and so reduce apoptosis and improve kidney functions.