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

• Published in: Biochimica et biophysica acta. General subjects Vol. 1866; no. 7; p. 130136
• Main Authors: Mazanova, Anna, Shymanskyi, Ihor, Lisakovska, Olha, Labudzynskyi, Dmytro, Khomenko, Anna, Veliky, Mykola
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2022
• Subjects: Animals; blood serum; Caspase 3; Cholecalciferol - pharmacology; Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Type 1 - complications; insulin-dependent diabetes mellitus; kidney diseases; kidneys; Nephropathy; NF-kappa B - metabolism; Nuclear factor kappa B (NF-κB); protein content; streptozotocin; Type 1 diabetes; Vitamin D - pharmacology; Vitamin D auto/para/endocrine system; Vitamin D3; Vitamins; Vitamin D3; Nuclear factor kappa B (NF-κB); Nephropathy; Vitamin D auto/para/endocrine system; Type 1 diabetes; Vitamin D
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2022.130136

Type 1 diabetes (T1D) is accompanied by numerous side effects, including renal dysfunction. Mounting evidence suggests that overactivation of nuclear factor ĸB (NF-κB) is one of the key triggers of diabetes-associated chronic kidney disease. Vitamin D3 is considered as a strong modulator of a number of transcription factors, including NF-κB. The purpose of our study was to assess the contribution of NF-κB to type 1 diabetes (T1D)-induced kidney dysfunction and to determine if vitamin D3 supplementation can correct the changes associated with T1D. 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 D3 (600 IU/kg b.w.), T1D group treated with NF-κB inhibitor – BAY 11‐7082. 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-κB and increased cleaved (p17) caspase-3 level in renal tissue. Restoration of vitamin D status normalized vitamin D-endocrine system, decreased NF-κB activation and caspase-3 protein level in the kidneys of diabetic animals. BAY 11–7082 partially mimicked the effects of vitamin D3. Vitamin D3 supplementation counteracts diabetes-induced kidney damage, most likely through VDR-mediated inhibition of NF-κB activation. [Display omitted] •Vitamin D3 can correct NF-ĸB associated kidney dysfunction.•Balanced D-endocrine system protects kidneys from NF-κB-mediated failure in diabetes.•NF-κB regulation by cholecalciferol is critical for diabetes nephropathy prevention.•NF-κB-mediated caspase 3 hyperactivation leads to kidney dysfunction in diabetes.