Furthermore, sestrin 2 expression was markedly decreased on day 42, when glomerulosclerosis and severe periglomerular fibrosis were observed. In PAN nephropathy, decreased sestrin 2 expression, increased P-S6RP expression, and periglomerular fibrosis were observed on day 9, when massive proteinuria developed, however, these changes
reversed nearly completely to baseline levels by day 28, by which time the proteinuria had also resolved. In anti-GBM nephritis, sestrin 2 expression was absent within the area of the crescents, whereas increased P-S6RP expression was observed in the cells within the crescents. To examine the role of sestrin in PECs, conditionally immortalized cultured PECs were silenced for sestrin 2 using specific shRNA. BI 6727 datasheet Sestrin 2-silenced PECs cultured under growth-restrictive conditions showed increased levels of phosphorylated 4E-BP1, p70S6K and S6RP and increased apoptosis. Conclusion: These data suggest that sestrin 2 is involved in PEC homeostasis through regulating the activity of mTOR. In addition, sestrin 2 could be a novel maker of PECs, and decreased expression of sestrin 2 might be a marker of PEC injury. HARA Target Selective Inhibitor Library cost SATOSHI1, KOBAYASHI NAMIKO1, MANABE SHUN1, SAKAMOTO KAZUO1, TAKASHIMA YASUTOSHI1, UENO TOSHIHARU1, HAMADA JURI2, MATSUSAKA TAIJI3, NAGATA MICHIO1 1Department of Kidney and Vascular Pathology, University of Tsukuba; 2Life Science
Center, Tsukuba Advanced Research Alliance, Graduate School of Life and Evironmental Sciences, University of Tsukuba;
3Department of Internal Medicine, Tokai University School of Medicine Introduction: Focal segmental glomerulosclerosis (FSGS) cellular variant is characterized these by endocapillary proliferation mainly composed of foam cells which are derived from macrophage, accompanying with extracapillary proliferation. The present study aimed to investigate how foam cells infiltrate into the glomerulus in the setting of podocyte injury. Methods: We generated NEP25/LDLRKO mice which are model of inducible podocyte-specific injury under hypercholesterolemia, using immunotoxin and western-type diet (WTD). Biochemistry and kidney pathology of NEP25/LDLRKO mice were compared with ones of LDLRKO mice and NEP25 mice. Oil red O (ORO) staining and immunostaining for CD68 and WT-1 were performed. Lipid components were analyzed using matrix-associated laser desorption/ionization-imaging mass spectrometry (IMS) in NEP25/LDLRKO mice compared with LDLRKO mice. Uninephrectomized LDLRKO mice were induced adriamycin nephropathy. Kidney pathology were analyzed in the group feeding WTD compared with the group feeding normal diet (ND). Immunostaining for oxidized phospholipid was performed. Results: NEP25/LDLRKO mice showed a few intraglomerular macrophage and foam cells infiltration, although no significant differences were noted. However, ORO-positive area in the glomeruli significantly increased in NEP25/LDLRKO mice (NEP25/LDLRKO 7.68 ± 2.07%, LDLRKO 0.24 ± 0.07%, NEP25 0.26 ± 0.05%; P = 0.