Fig 1: MPEP decreases SORT1 expression and increases extracellular PGRN in mammalian cell lines. (A and B) M17 cells were treated with control siRNA (siR-Ctrl) or gene-specific SORT1 siRNA (siR-SORT1). (A) Intracellular levels of PGRN, SORT1 and GAPDH were evaluated by western blot at a 48 h time-point. (B) Suppression of SORT1 levels increased extracellular PGRN levels. (C) Chemical name and structure of MPEP. (D–I) Treatment of M17 cells (D and E), HeLa cells (F and G) or NIH3T3 cells (H and I) with MPEP for 24 h dose dependently reduced SORT1 levels (D, F and H) and increased exPGRN levels (E, G and I) at 10 and 20 µM. (J) Under the same conditions, MPEP did not affect levels of SORLA, SORCS1 and ubiquitinated proteins in M17 cells. ***P < 0.001 versus vehicle control, analysis performed by one-way ANOVA followed by Tukey's post-test.