Lipid dysmetabolism is one of the main features of diabetes mellitus and manifests by dyslipidemia as well as the ectopic accumulation of lipids in various tissues and organs,including the kidney.Research suggests tha...Lipid dysmetabolism is one of the main features of diabetes mellitus and manifests by dyslipidemia as well as the ectopic accumulation of lipids in various tissues and organs,including the kidney.Research suggests that impaired cholesterol metabolism,increased lipid uptake or synthesis,increased fatty acid oxidation,lipid droplet accumulation and an imbalance in biologically active sphingolipids(such as ceramide,ceramide-1-phosphate and sphingosine-1-phosphate)contribute to the development of diabetic kidney disease(DKD).Currently,the literature suggests that both quality and quantity of lipids are associated with DKD and contribute to increased reactive oxygen species production,oxidative stress,inflammation,or cell death.Therefore,control of renal lipid dysmetabolism is a very important therapeutic goal,which needs to be archived.This article will review some of the recent advances leading to a better understanding of the mechanisms of dyslipidemia and the role of particular lipids and sphingolipids in DKD.展开更多
Idiopathic membranous nephropathy (IMN) is a Th2 nephritogenic immune disorder. It is caused by the accumulation of immune complexes, mainly IgG4, at the basal glomerular membrane that leads to the damage of the glome...Idiopathic membranous nephropathy (IMN) is a Th2 nephritogenic immune disorder. It is caused by the accumulation of immune complexes, mainly IgG4, at the basal glomerular membrane that leads to the damage of the glomerular barrier and subsequent injury of podocytes. Our aim was to evaluate the relationship between cytokine polymorphisms and IMN. We investigated the cytokine polymorphisms in forty-five patients and one hundred twenty-four healthy individuals, using polymerase chain reaction-sequence specific primers (PCR-SSP). We showed a significant increase in allelic frequencies of the alleles -590T and -33T of IL-4 gene and -308A of TNF-α gene, in IMN patients. In addition, we observed an increased frequency of allele -1082G in IL-10 gene in a subgroup of patients with CD4/CD8 ratio major than 2, when compared either to control subjects or the subgroup of patients with CD4/CD8 ratio minor than 2. Moreover, analyzing the Th1/Th2 cytokines in serum and urine, we found increased levels of IL-4 in serum and IL-5 in urine of patients. We deduce that the alleles -590T and -33T of IL-4 and -308A of TNF-α may be associated with IMN. In addition, in patients with increased T helper lymphocytes, IL-10 -1082G polymorphism can also play a role in the pathogenesis of the disease. These findings remark the role of Th2 immune response and suggest the association between polymorphic variants of IL-4, IL-10 and TNF-α genes with the development of IMN and therefore giving a better insight in pathogenesis of this disease.展开更多
基金the National Institute of Health(Research in Dr.Alessia Fornoni’s laboratory),No.R01DK117599,No.R01DK104753,No.R01CA227493,No.U54DK083912,No.UM1DK100846,and No.U01DK116101the Miami Clinical Translational Science Institute,No.UL1TR000460and the Chernowitz Medical Research Foundation(Mitrofanova A and Burke G),No.GR016291.
文摘Lipid dysmetabolism is one of the main features of diabetes mellitus and manifests by dyslipidemia as well as the ectopic accumulation of lipids in various tissues and organs,including the kidney.Research suggests that impaired cholesterol metabolism,increased lipid uptake or synthesis,increased fatty acid oxidation,lipid droplet accumulation and an imbalance in biologically active sphingolipids(such as ceramide,ceramide-1-phosphate and sphingosine-1-phosphate)contribute to the development of diabetic kidney disease(DKD).Currently,the literature suggests that both quality and quantity of lipids are associated with DKD and contribute to increased reactive oxygen species production,oxidative stress,inflammation,or cell death.Therefore,control of renal lipid dysmetabolism is a very important therapeutic goal,which needs to be archived.This article will review some of the recent advances leading to a better understanding of the mechanisms of dyslipidemia and the role of particular lipids and sphingolipids in DKD.
文摘Idiopathic membranous nephropathy (IMN) is a Th2 nephritogenic immune disorder. It is caused by the accumulation of immune complexes, mainly IgG4, at the basal glomerular membrane that leads to the damage of the glomerular barrier and subsequent injury of podocytes. Our aim was to evaluate the relationship between cytokine polymorphisms and IMN. We investigated the cytokine polymorphisms in forty-five patients and one hundred twenty-four healthy individuals, using polymerase chain reaction-sequence specific primers (PCR-SSP). We showed a significant increase in allelic frequencies of the alleles -590T and -33T of IL-4 gene and -308A of TNF-α gene, in IMN patients. In addition, we observed an increased frequency of allele -1082G in IL-10 gene in a subgroup of patients with CD4/CD8 ratio major than 2, when compared either to control subjects or the subgroup of patients with CD4/CD8 ratio minor than 2. Moreover, analyzing the Th1/Th2 cytokines in serum and urine, we found increased levels of IL-4 in serum and IL-5 in urine of patients. We deduce that the alleles -590T and -33T of IL-4 and -308A of TNF-α may be associated with IMN. In addition, in patients with increased T helper lymphocytes, IL-10 -1082G polymorphism can also play a role in the pathogenesis of the disease. These findings remark the role of Th2 immune response and suggest the association between polymorphic variants of IL-4, IL-10 and TNF-α genes with the development of IMN and therefore giving a better insight in pathogenesis of this disease.
