High glucose upregulates CYP24A1 expression which attenuates the ability of 1,25(OH)2D3 to increase NGF secretion in a rat Schwann cell line RSC96

• High glucose attenuates NGF secretion stimulated by 1,25(OH)2D3 in Schwann cells.
• High glucose upregulates the expression of CYP24A1 gene and protein.
• Genistein downregulates CYP24A1 and increases NGF secretion led by 1,25(OH)2D3 in high glucose-treated Schwann cells.
• CYP24A1 gene silencing attenuates the effect of high glucose on NGF secretion mediated by 1,25(OH)2D3.
• Upregulation of CYP24A1 gene by high glucose may be independent of ROS.

Vitamin D deficiency or insufficiency is an independent risk factor for diabetic peripheral neuropathy (DPN), but the relationship between 1,25(OH)2D3 and DPN remains unknown. We found that 1,25(OH)2D3 stimulated the secretion of nerve growth factor (NGF) in rat Schwann cell line RSC96, but ability of 1,25(OH)2D3 to increase NGF protein was impaired under high glucose conditions. High glucose upregulated the expression of CYP24A1 protein, which catalyzes the conversion of 1,25(OH)2D3 into inactive products, further impairing the ability of 1,25(OH)2D3 to upregulate NGF secretion in Schwann cells. Inhibition of CYP24A1 protein expression ameliorated the secretion of NGF in response to 1,25(OH)2D3. The findings of this study suggest that CYP24A1 protein plays an important role in the relationship between DPN and 1,25(OH)2D3.