Role of COX-2/mPGES-1/Prostaglandin E2 Cascade in Kidney Injury

COX-2/mPGES-1/PGE2 cascade plays critical roles in modulating many physiological and pathological actions in different organs. In the kidney, this cascade is of high importance in regulating fluid metabolism, blood pressure, and renal hemodynamics. Under some disease conditions, this cascade displays various actions in response to the different pathological insults. In the present review, the roles of this cascade in the pathogenesis of kidney injuries including diabetic and nondiabetic kidney diseases and acute kidney injuries were introduced and discussed. The new insights from this review not only increase the understanding of the pathological role of the COX-2/mPGES-1/PGE2 pathway in kidney injuries, but also shed new light on the innovation of the strategies for the treatment of kidney diseases

Rotenone Remarkably Attenuates Oxidative Stress, Inflammation, and Fibrosis in Chronic Obstructive Uropathy

Mitochondrial abnormality has been shown in many kidney disease models. However, its role in the pathogenesis of chronic kidney diseases (CKDs) is still uncertain. In present study, a mitochondrial complex I inhibitor rotenone was applied to the mice subjected to unilateral ureteral obstruction (UUO). Following 7-days rotenone treatment, a remarkable attenuation of tubular injury was detected by PAS staining. In line with the improvement of kidney morphology, rotenone remarkably blunted fibrotic response as shown by downregulation of fibronectin (FN), plasminogen activator inhibitor-1 (PAI-1), collagen I, collagen III, and α-SMA, paralleled with a substantial decrease of TGF-β1. Meanwhile, the oxidative stress markers thiobarbituric acid-reactive substances (TBARS) and heme oxygenase 1 (HO-1) and inflammatory markers TNF-α, IL-1β, and ICAM-1 were markedly decreased. More importantly, the reduction of mitochondrial DNA copy number and mitochondrial NADH dehydrogenase subunit 1 (mtND1) expression in obstructed kidneys was moderately but significantly restored by rotenone, suggesting an amelioration of mitochondrial injury. Collectively, mitochondrial complex I inhibitor rotenone protected kidneys against obstructive injury possibly via inhibition of mitochondrial oxidative stress, inflammation, and fibrosis, suggesting an important role of mitochondrial dysfunction in the pathogenesis of obstructive kidney disease

Correlation between PPAR Gene Polymorphisms and Primary Nephrotic Syndrome in Children

Pediatric primary nephrotic syndrome (PNS) is a chronic disease promoted by metabolic and immune dysfunctions. Peroxisome proliferator-activated receptor (PPAR) polymorphisms have been associated with a variety of metabolic and kidney disorders. We therefore hypothesized that PPAR polymorphisms might be involved in the pathophysiology of PNS. We compared the distributions of the PPAR-γ Pro12Ala and Val290Met, PPAR-γ coactivator-α (PGC-1α) Gly482Ser, and PPAR-α Leu162Val single nucleotide polymorphisms (SNPs) between children with PNS and normal controls and analyzed their correlations with clinical and metabolic indicators and steroid responsiveness. There were no significant differences in distributions of any of the polymorphisms between PNS cases and controls. However, PNS patients with the PPAR-γ (Pro12Ala) PP genotype had significantly higher fasting serum insulin, IgA, and HOMA-IR levels and lower insulin sensitivity than did patients with PA and AA genotypes. Additionally, the PGC-1α (Gly482Ser) A allele was associated with lower CD8+ T-cell counts and higher triglyceride and complement C3 levels compared with the G allele. No polymorphisms were related to hormone sensitivity. These results suggest that the PPAR-γ (Pro12Ala) and PGC-1α (Gly482Ser) SNPs may influence insulin and triglyceride metabolism in children with PNS and may thus be relevant to the prognosis of this chronic condition