Background

Diabetic kidney disease (DKD) remains one of the main causes of end-stage renal disease (ESRD) and mortality in diabetic patients worldwide. Vitamin D deficiency (VitDD) is one of the main consequences of different chronic kidney disease (CKD) types and is associated with rapid progression to ESRD. Nevertheless, the mechanisms that lead to this process are poorly understood. This study aimed to characterize a model of diabetic nephropathy progression in VitDD and the epithelial-mesenchymal-transition (EMT) role in these processes.

Methods

Wistar Hannover rats received a diet with or without VitD before type 1 diabetes (T1D) induction. After this procedure, the rats were accompanied for 12 and 24 weeks after T1D induction and the renal function, structure, cell transdifferentiating markers and zinc finger e-box binding homeobox 1/2 (ZEB1/ZEB2) contribution to kidney damage were evaluated during the DKD progression.

Results

The results showed an increase in glomerular tuft, mesangial and interstitial relative areas and renal function impairment in VitD-deficient diabetic rats compared to diabetic rats that received a VitD-containing diet. These alterations can be associated with increased expression of EMT markers, ZEB1 gene expression, ZEB2 protein expression and TGF-β1 urinary excretion. Decreased miR-200b expression, an important post-transcriptional regulator of ZEB1 and ZEB2 was also observed.

Conclusion

Our data demonstrated that VitD deficiency contributes to the rapid development and progression of DKD in diabetic rats induced by increase ZEB1/ZEB2 expressions and miR-200b downregulation.

中文翻译：

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维生素 D 缺乏通过增加 ZEB1/ZEB2 表达导致糖尿病肾病进展

背景

糖尿病肾病（DKD）仍然是全世界糖尿病患者终末期肾病（ESRD）和死亡的主要原因之一。维生素 D 缺乏 (VitDD) 是不同类型慢性肾脏病 (CKD) 的主要后果之一，并且与 ESRD 的快速进展相关。然而，人们对导致这一过程的机制知之甚少。本研究旨在表征 VitDD 中糖尿病肾病进展的模型以及上皮间质转化 (EMT) 在这些过程中的作用。

方法

Wistar Hannover大鼠在诱导 1 型糖尿病 (T1D) 之前接受含或不含 VitD 的饮食。在此过程后，大鼠在 T1D 诱导后陪伴 12 周和 24 周，并评估肾功能、结构、细胞转分化标记物和锌指 e-box 结合同源框 1/2 (ZEB1/ZEB2) 对肾脏损伤的贡献。 DKD 进展。

结果

结果显示，与接受含 VitD 饮食的糖尿病大鼠相比，缺乏 VitD 的糖尿病大鼠的肾小球簇、系膜和间质相关面积有所增加，肾功能受损也有所增加。这些改变可能与 EMT 标记物表达、ZEB1 基因表达、ZEB2 蛋白表达和 TGF-β1 尿排泄增加有关。还观察到 miR-200b 表达减少，miR-200b 是 ZEB1 和 ZEB2 的重要转录后调节因子。

结论

我们的数据表明，VitD 缺乏通过 ZEB1/ZEB2 表达增加和 miR-200b 下调诱导糖尿病大鼠 DKD 的快速发展和进展。