The link between vitamin D status and NF-cB-associated renal dysfunction in experimental diabetes mellitus

Background: Type 1 diabetes (T1D) is accompanied by numerous side effects, including renal dysfunction. Mounting evidence suggests that overactivation of nuclear factor rcB (NF-kappa B) is one of the key triggers of diabetes associated chronic kidney disease. Vitamin D-3 is considered as a strong modulator of a number of transcription factors, including NF-cB. The purpose of our study was to assess the contribution of NF-kappa B to type 1 diabetes (T1D)-induced kidney dysfunction and to determine if vitamin D-3 supplementation can correct the changes associated with T1D. Methods: The following animal groups were used: control, diabetic (induced by single i.p. injection of streptozocin at dose 55 mg/kg b.w.), T1D group treated with vitamin D-3 (600 IU/kg b.w.), T1D group treated with NF-kappa B inhibitor BAY 11-7082. Results: Diabetes led to a decrease in serum 25(OH)D that was accompanied by down-regulation of vitamin D receptor (VDR) expression and up-regulation of hydroxylases CYP24A1 and CYP27B1 synthesis in the kidneys. Diabetes activated the transcription factor NF-kappa B and increased cleaved (p17) caspase-3 level in renal tissue. Restoration of vitamin D status normalized vitamin D-endocrine system, decreased NF-kappa B activation and caspase3 protein level in the kidneys of diabetic animals. BAY 11-7082 partially mimicked the effects of vitamin D-3. General significance: Vitamin D3 supplementation counteracts diabetes-induced kidney damage, most likely through VDR-mediated inhibition of NF-kappa B activation.