Background
Ureteral obstruction causes injury of the renal tissues and can irreversibly progress to renal fibrosis, with atrophy and apoptosis of tubular cells. The goal of the current study was to examine the effects of rhein on the apoptosis o renal tubular cells as well as renal fibrosis using a rodent model of unilateral ureteral obstruction (UUO).
Methods
UUO was induced through ureteral ligation, then animals received treatments with rhein or vehicle. The control rats only received sham operation. The renal tissue was harvested 1 week after surgery for assessment of kidney fibrosis.
Results
The expressions of collagen I and α-smooth muscle actin (α-SMA), as well as the severity of renal tubular apoptosis and fibrosis were time-dependently increased following UUO. Treatments with rhein partially inhibited such responses. Renal interstitial fibrosis was associated with STAT3 (signal transducer and activator of transcription 3) phosphorylation as well as altered expressions of Bax and Bcl2, both apoptosis-related proteins. Treatment with rhein also partly blocked these responses.
Conclusion
These findings demonstrated that rhein mitigated apoptosis of renal tubular cell as well as renal fibrosis in a UUO rodent model. This curative effect is likely mediated via suppression of STAT3 phosphorylation.
<b><i>Introduction:</i></b> Obesity is a major risk factor for metabolic disorders in children. Therefore, it is particularly important to study the abnormal regulation of circulating miR-24-3p in obese children and its predictive value for metabolic syndrome. <b><i>Methods:</i></b> Serum samples were obtained from children with obesity (<i>n</i> = 45), obese children with metabolic syndrome (<i>n</i> = 52), and healthy controls (<i>n</i> = 50). The expression levels of miR-24-3p were detected by reverse transcription quantitative PCR. The ROC curve was used to evaluate the diagnostic value of miR-24-3p. Pearson’s correlation analysis was performed to evaluate the relationship between serum miR-24-3p and different clinical parameters. Logistic regression analysis was used to evaluate the relationship between miR-24-3p and obesity with metabolic syndrome in children. <b><i>Results:</i></b> The expression of miR-24-3p was the highest in obese children with metabolic syndrome. ROC results showed that miR-24-3p had the ability to distinguish healthy individuals from obese children (area under the curve [AUC] = 0.951) and can predict the occurrence of metabolic syndrome for obese children (AUC = 0.890). The expression level of miR-24-3p was positively correlated with body mass index (<i>r</i> = 0.817, <i>p</i> < 0.001), fasting blood glucose (<i>r</i> = 0.798, <i>p</i> < 0.001), triglycerides (<i>r</i> = 0.773, <i>p</i> < 0.001), systolic blood pressure (<i>r</i> = 0.746, <i>p</i> < 0.001), and diastolic blood pressure (<i>r</i> = 0.623, <i>p</i> < 0.001), respectively. Logistic regression analysis showed that miR-24-3p was an independent influence factor for the occurrence of metabolic syndrome in obese children. <b><i>Discussion/Conclusion:</i></b> MiR-24-3p is a potential noninvasive marker for children with obesity and has predictive value for the occurrence of metabolic syndrome.
Nudel is a newly discovered factor related to cell migration. The tubular epithelial-mesenchymal transition (EMT) includes four steps: the loss of the adhesive properties of epithelial cells, the acquisition of a mesenchymal cell phenotype, the destruction of the tubular basal membrane, and the migration into the renal interstitium. The purpose of this study was to investigate the role of Nudel in the high-glucose-induced EMT of tubular epithelial cells. Human renal proximal tubular epithelial cells (HKCs) were treated with Nudel shRNA to clarify the role and mechanism of Nudel in tubular EMT induced by high glucose. We found that Nudel was expressed at a high level in high-glucose-stimulated HKCs, and the expression of Nudel was associated with the activation of signal transducer and activator of transcription 3. After transfection with Nudel shRNA, we detected the expression levels of E-cadherin, α-smooth muscle actin (α-SMA), and the Wiskott-Aldrich syndrome family of proteins (including WASP, N-WASP, WAVE1, WAVE2, and WAVE3) via assay. Cell migration was analyzed by the scratching method. The results showed that high glucose downregulated E-cadherin expression, upregulated α-SMA expression, and promoted the migration of HKCs. The expression levels of N-WASP, WAVE1, and WAVE2 were also elevated in HKCs treated with high glucose. All changes induced by high glucose were ameliorated by Nudel depletion. We conclude that Nudel participates in the transition and the migration of tubular epithelial cells via the regulation of WASP family proteins.
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