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A. Khaibullina et al.
cant differences in mesangial cell proliferation, or that fac- tors other than MSP1 could stimulate mesangial growth in SCD mice. Thus, we hypothesized that MSP1 played a role in the activation of endothelial cells. The effect of MSP1 on renal glomerular endothelial cells is still not known.
To test the effect of MSP1 on endothelium, we used cul- tured HGEC. MSP1 had previously been shown to stimu- late motility of murine resident peritoneal macrophages
and kidney epithelial cells.18,46 We demonstrated that MSP1 treatment increased motility of HGECs and induced formation of F-actin stress fibers that is essential for motil- ity and permeability of endothelial cells.32 Further studies are needed to determine whether MSP1/RON signaling induces permeability of cultured endothelial cells. Interestingly, MSP1 increased vWF expression levels in HGEC. High levels of vWF were also found in SCD murine glomeruli. RONi treatment reduced endothelial
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EFGH
P=3x10-8 P=2x10-7 P=0.002 P=0.04
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Figure 8. Treatment of sickle cell disease (SCD) mice with RON inhibitor (RONi) reduces renal endothelial injury. Representative pictures of renal sections of control and SCD mice treated with either RONi or vehicle (DMSO) are shown. (A) Hematoxylin&Eosin (H&E) staining. (B) Periodic Acid-Schiff (PAS) staining. (C) von Willebrand factor (vWF) immunostaining (red). (D) Intercellular Adhesion Molecule (ICAM) immunostaining (red). Bar sizes 50μm. (E and F) Quantification of glomeruli size (E) and capillary size per glomeruli cross section (F) is performed using CellSens Standard software. (G and H) Quantification of vWF (G) and ICAM (H) expression in glomeruli cross sections is performed using ImageJ Fiji version software. Six mice per group were used for each staining. Each dot represents a value obtained from one glomerulus cross-section. For quantification graphs, means are shown.
haematologica | 2018; 103(5)