? em P /em ? ?0.05 versus the controls. expression of adhesion molecules and chemokines in?glomerular resident cells. Focal segmental glomerulosclerosis (FSGS) is a progressive kidney disease caused by podocyte injury.1C4 The pathology of FSGS includes a variety of glomerular features. The Columbia classification system divides FSGS into the following five variants: not otherwise specified, perihilar variant, cellular variant, tip variant, and collapsing variant.1,5,6 The classification is useful for predicting the prognosis in FSGS.1,5C7 Glomerulosclerosis is defined by its pathological characteristics, including capillary collapse accompanied by deposition of extracellular matrices and/or hyaline materials. This classic feature of sclerosis is usually observed in not otherwise specified and perihilar variants, whereas it is not observed in the definition of other variants. To diagnose FSGS in the absence of classic sclerosis, the infiltration of foam cells Troxerutin in the glomerular segment is a good marker, particularly in cellular variants.1,7 Although glomerular foam cells can be observed in any variant of FSGS and are thought to be involved in disease progression, the mechanism underlying foam cell infiltration in FSGS remains largely unknown. Studies have shown that glomerular foam cells were associated with extremely high levels of serum lipids in patients with familial hypercholesterolemia and lecithin-cholesterol acyltransferase deficiency.8,9 Glomerular foam cells were also observed in experimental models of hypercholesterolemia, 10C15 suggesting that high levels of serum lipids may be a plausible basis for glomerular foam cell infiltration. Some studies reported that glomerular foam cells were associated with nephrotic syndrome in humans, including membranous glomerulonephritis, diabetic nephropathy, and IgA glomerulonephritis.16C18 However, in these cases, the glomerular foam cells were not always associated with hyperlipidemia. A previous study demonstrated that glomerular foam cells were not correlated with serum cholesterol levels in FSGS patients.7 Likewise, glomerular foam cells were absent in MAPKAP1 minimal change disease, despite the presence of similar levels of serum lipids observed in FSGS.19 These findings suggest that additional factors other than serum lipid levels may account for the formation of glomerular foam cells in FSGS. The characteristic histology of glomerular foam cell formation in FSGS is its segmental and intracapillary localization associated with overlaying podocyte abnormalities. Because podocyte injury represents the common basis of FSGS, there may be a causal relationship between podocyte injury and foam cell accumulation in Troxerutin particular variants of FSGS. Most glomerular foam cells are derived Troxerutin from CD68-positive macrophages,20,21 which transform into foam cells by ingesting lipids within the glomerulus study to assess changes in the molecular profiles of mesangial cells and endothelial cells in response to podocyte injuryCdriven lipid modifications. Our results suggest that podocyte injury promotes hypercholesterolemia-based lipid deposition and specific peroxidation, which activate a molecular network within a glomerular microenvironment that induces macrophage recruitment and foam cell formation in FSGS. Materials and Methods Animal Troxerutin Experiments NEP25 Mice NEP25 mice (C57BL/6 background) genetically expressing human CD25 in podocytes were used.3,4,25 In this model, injection of the immunotoxin for human CD25 (LMB2) provokes podocyte-specific injury. Troxerutin Because LMB2 does not damage mouse CD25 but human CD25, LMB does not affect any other organs, including the immune system, except for kidney in mice. Mice aged between 8 and 12 weeks were i.v. injected with LMB2 [4 ng/g body weight (BW) diluted in 100 L of phosphate-buffered saline (PBS) containing 0.1% bovine serum albumin] or vehicle (VH) through the tail vein. The mice.