| Background:Minimal change disease (MCD) is a common type of nephrotic syndrome. It is characterized by extensive fusion and depletion of foot processes of podocytes under electron microscope. Consequently, the damage of podocytes exerts pivotal effects toward the pathogensis and progression of MCD. Angiopoietin-like4(Angptl4), a member of angiopoietin-like protein family, plays participating role in the glucose and lipid metabolism, tumor metabolism, atherosclerosis and angiogenesis. In recent years, studies have demonstrated that Angptl4participated in podocyte injury, leading to progression of nephropathy.Objective:To compare and analyze the concentration of Angptl4in plasma and urine from patients diagnosed as podocyte injury associated nephrotic syndrome, non-nephrotic syndrome with podocyte injury, IgA nephropathy and normal case, respectively. The expression levels of Angptl4in podocytes and kidneys from rat models were detected to determine its expression features. Additionally, methylprednisolone was administrated to the MCD rat models to further investigate the potentially protective effects of methylprednisolone toward MCD in rats. Methods:I. The concentration of Angptl4in plasma and urine from patients with different pathologic type of nephropathy.Patients included were grouped as podocyte injury associated nephrotic syndrome (NS), non-nephrotic syndrome with podocyte injury (non-NS), IgA nephropathy (IgAN) and normal case, respectively. The plasma and urine samples from patients were collected to perform ELISA to determine and compare the concentration of Angptl4in different cases. Analysis the characteristics of Angptl4expression combine with electron microscopy observation and urinary protein level.II. MCD rat models and the treatment.The rats used in this study were randomly divided into three groups:control group, MCD model group and methylprednisolone-treated MCD group. Simultaneously, puromycin aminonucleoside (PAN) was given intravenously to the MCD model rats and methylprednisolone-treated MCD rats at the same dose, respectively. In addition, the kidneys, serum and urine samples of model rats were collected at each time point to evaluate the changes of corresponding biochemical indicators, such as urinary protein, serum albumin, blood triglyceride and cholesterol. The concentration of Angptl4at both serum and urine levels was determined by ELISA.III. The expression levels of Angptl4in podocytes and kidneys from rat modelsAfter being grown to confluence, podocytes were administrated with PAN. And normal culture medium was given to the same cell line as control. The morphology of cyto skeleton and the Angptl4expression were accessed by Immunofluorescence. The actin cytoskeleton was stained in green with phalloidin and Angptl4were stained in red by Alexa Fluor(?)568. Furthermore, immunohistochemistry was performed to evaluate the expression of Angptl4in the kidney tissue sections collected from control group, MCD model group and methylprednisolone-treated MCD group. Results:The concentration of plasma Angptl4significantly decreased in NS and non-NS group compared with IgAN and control group. The Angptl4level in urine markedly up-regulates in NS, non-NS and IgAN group compared with control group. The Angptl4urine concentration of NS group is much higher than the other groups.In addition,the concentration of plasma Angptl4decreased in those whose podocyte foot process is diffuse effacement, while the Angptl4urine concentration increased significantly.In MCD rat models, increased levels of urinary protein, blood triglyceride and cholesterol were observed in MCD model group, whose serum albumin level significantly decreased compared with control group. Administration of methylprednisolone result in remarkable decline in urinary protein, blood triglyceride and cholesterol levels. Moreover, it could also up-regulate the serum albumin level of rat models. Significant decrease in serum Angptl4in MCD model group was detected when compared with control group. Urine level of Angptl4significantly increased in model group compared with control group. Methylprednisolone treatment could lead to marked attenuation of urine Angptl4level.Remarkable fracture and restructuring of cytoskeleton were observed in podocytes treated with PAN. When compared with control group, the expression of Angptl4significantly increased in PAN-treated podocytes in addition to the changes in cytoskeleton. The tissue section of MCD rat models showed immunohistochemical strong expression of Angptl4in the glomerulus than that in control rats. And administration of methylprednisolone was able to attenuate the Angptl4expression.Conclusion:In summary, our data demonstrates that the distinctive expression pattern of Angptl4is correlated with podocyte injury, contributing to the progression of nephropathy. Besides, the urine Angptl4level is positively correlated with severity of podocyte injury.In MCD rat models, administration of methylprednisolone is able to remarkably attenuate the proteinuria and reduce the serum albumin and blood triglyceride. Additionally, up-regulated expression of Angptl4, specially expressed in glomerulus podocytes, is found in the cases of podocyte injury. Furthermore, methylprednisolone treatment leads to significant decrease of Angptl4expression.Therefore, the up-regulation of Angptl4plays a crucial role in the podocyte injury, contributing to the pathogensis and progression of MCD. Administration of methylprednisolone can exert a protective effect towards podocyte injury and may serve as a promising approach in therapy for MCD. |
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