Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The proteinuria-induced apoptosis of proximal tubular cells (PTCs) plays a crucial role in renal tubulointerstitial injury in chronic kidney disease. Recent studies have shown that endoplasmic reticulum (ER) stress is involved in proteinuria-induced apoptosis of PTCs. Our study showed that albumin overload led to ER stress, CCAAT/enhancer-binding protein-homologous protein (CHOP), and PKR-like kinase (PERK) activation and to apoptosis of PTCs in proteinuria patients. The apoptotic index of proximal renal tubular cells in the nephrotic kidneys was about 13-fold higher than that in control kidneys. The increased tubular expression of GRP78, ORP150, and CHOP and nuclear localization of CHOP in nephrotic kidneys were also detected. The expression of GRP78, CHOP, PERK, and phosphorylated PERK increased proportionately with HSA overload in a dose- and time-dependent manner. Knockdown of CHOP by siRNA significantly reduced the HSA-induced apoptosis of HKC. The expression of PERK did not significantly change, but the phosphorylation of PERK increased. Furthermore, knockdown of PERK significantly inhibited HSA-induced CHOP expression, suppressing apoptosis in HKCs by 2.48-fold compared to controls. Overexpression of CHOP enhanced the apoptosis of HKC induced by albumin, no significant difference was observed in the expression of PERK, whereas the phosphorylation of PERK decreased. Our data indicated that proteinuria induces ER stress in renal tubular cells, which may subsequently lead to tubular damage through a PERK-CHOP-dependent pathway. This ER stress-induced apoptosis pathway may contribute to renal tubulointerstitial injury by proteinuria in chronic kidney disease.
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PMID:Albumin overload induces apoptosis in renal tubular epithelial cells through a CHOP-dependent pathway. 2014 29

The 150-kDa oxygen-regulated protein (ORP150) belongs to a family of the heat shock protein implicated in the cellular response to environmental stress. Previous data demonstrated that ORP150 regulates the secretion of vascular endothelial growth factor (VEGF) to drive progression of angiogenesis associated with proliferative diabetic retinopathy. However, the expression and biological functions of serum ORP150 levels in diabetic nephropathy (DN) remain unclear. In this study, we reported for the first time that ORP150 was up-regulated in serum of patients with DN. Moreover, we observed the dramatic increase in serum ORP150 accompanied with the elevated levels of proteinuria and serum VEGF levels in DN, indicating the possible involvement of ORP150 in regulation of albuminuria via mediating VEGF in DN. Employing the streptozotocin (STZ) to construct the DN model, we confirmed the positive correlation of ORP150 with VEGF in vivo. Monoclonal anti-ORP150 antibodies treatment significantly decreased the secretion of VEGF and albuminuria in STZ-induced DN models. Consequently, our data suggested that ORP150 levels were positively correlated with proteinuria burden via mediating VEGF in DN. It may be considered as a novel diagnostic and therapeutic target.
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PMID:The 150-kDa oxygen-regulated protein (ORP150) regulates proteinuria in diabetic nephropathy via mediating VEGF. 3102 25