Vitamin D deficiency contributes to the diabetic kidney disease progression via increase ZEB1/ZEB2 expressions

Abstract

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.

Construction of a Nomogram-Based Prediction Model for the Risk of Diabetic Kidney Disease in T2DM

“…However, it is indisputable that correcting Vit D can still play a role in delaying the development of DKD. 40 , 41 …”

“…However, it is indisputable that correcting Vit D can still play a role in delaying the development of DKD. 40,41 We should acknowledge several limitations of this study. First, this was a single-center retrospective study, which inevitably had a certain selection bias.…”

Effects of vitamin family members on insulin resistance and diabetes complications

“…Vitamin D also improves blood glucose and insulin levels, reduces NF-kB activity in heart tissue, and down-regulates advanced glycosylation end products and the hexosamine pathway to alleviate diabetic cardiomyopathy[ 17 ]. In diabetic kidney disease (DKD), vitamin D deficiency up-regulates zinc finger e-box binding homeobox and down-regulates miR-200b, which promotes the epithelial-mesenchymal transformation process and changes the renal structure and function of diabetic rats to accelerate DKD development[ 18 ]. Vitamin D supplementation can effectively reduce albuminuria and creatinine, markers of kidney disease in diabetic nephropathy patients[ 19 ].…”

Insufficient Plasma Melatonin and Its Association With Neuropsychiatric Impairments in Patients With T2DM

“…Type 2 diabetes mellitus (T2DM) diabetes is a metabolic disease characterized by hyperglycemia, constituting a major global health threat as the ninth leading cause of death in the world [ 1 ]. In addition to the symptoms of increased blood sugar, insulin resistance, and metabolic disorders brought about by T2DM itself, increasing data have suggested the detrimental effect of T2DM on the structural and functional impairments of the brain, leading to various complications including stroke, cognitive impairment, depression, and even diabetic encephalopathy [ 2 , 3 ]. It is well known that metabolic disorders of glucose and lipids are risk factors for the dysfunctional changes of the brain, damaging the endothelial cells, resulting in cerebrovascular blockage or rupture, eventually causing morphological and functional changes, accompanied with the declines in attention, memory, and executive functions [ 4 ].…”