Active Vitamin D3 Protects Against Diabetic Kidney Disease by Regulating the JNK Signaling Pathway in Rats

Diabetic kidney disease (DKD) is an inflammatory disease caused by metabolic disorder. As an important signaling pathway in the inflammatory response, the JNK signaling pathway plays an crucial role in kidney injury in DKD. Vitamin D3 can reduce the inflammatory reaction and delay or even reverse DKD progression. Unfortunately, the mechanism by which vitamin D3 regulates DKD pathogenesis is unclear. This research established a DKD rat model and vitamin D3 and irbesartan were used as interventions. Then, urine and blood biochemistry; and inflammatory cytokine (IL-1 and IL-6), phosphorylated JNK pathway protein (MEK-4 and JNK1/2/3) and downstream factor (AP-1 and ATF-2) expression were assessed. We found that the DKD group showed body weight and insulin secretion were significantly decreased; significantly increased FPG, HOMA-IR and blood lipids; and significantly increased 24-h urinary protein (UPro) compared with normal group. Additionally, the levels of IL-1 and IL-6 and phosphorylated JNK pathway proteins were significantly elevated. These changes were improved by vitamin D3, especially at a low dosage. These results suggest that active vitamin D3 protects against DKD in rats by reducing IL-6 and IL-1 release, downregulating the JNK inflammatory signaling pathway, and inhibiting downstream transcription factor AP-1- and ATF-2-mediated kidney damage. This research provides a new theoretical support for vitamin D3 treatment of diabetic nephropathy.