PEDF relieves kidney injury in type 2 diabetic nephropathy mice by reducing macrophage infiltration.

Background: Pigment epithelium-derived factor (PEDF) is a multifunctional protein with anti-angiogenic, antioxidant and anti-inflammatory properties. PEDF is involved in the pathogenesis of diabetic retinopathy, but its exact role in diabetic kidney remains unclear. The present study aimed to investigate whether PEDF can alleviate renal damage in type 2 diabetic nephropathy mice by inhibiting macrophage infiltration. Methods: The db/db mice were randomly divided into diabetes PEDF intervention group (DM-P78-PEDF), diabetes empty carrier intervention group (DM-Vehicle) and diabetes mellitus group (DM). Subsequently, they were injected subcutaneously P78-PEDF (0.3μg/g/d) and PBS for 6 weeks. The kidney weight to body weight ratio was observed of the rats. Automatic biochemical analyzer to determine fasting blood glucose (GLU), blood urea nitrogen (UREA), serum creatinine (CREA), hemoglobin (HGB) content. Histological and ultrastructural pathologic changes in the kidneys were examined through H&E and PAS staining. Kidney tissues levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interferon gamma (IFN-γ) were determined by ELISA. Expression of the macrophages infiltration and typing as well as that of PEDF, NF-κB, TLR4 was evaluated in the kidneys. Results: PEDF was located in glomeruli and the expression of PEDF protein and mRNA in kidney of diabetic mice was declined significantly. Compared with diabetic mice treated with vehicle, continuous infusion of P78-PEDF could reduce blood urea nitrogen, serum creatinine (CREA), renal macrophage recruitment, inflammatory cytokines, histological changes and restore the expression of TLR4/NF-κB signaling pathway related factors in diabetic mice. Conclusion: These findings highlight the importance of P78-PEDF peptide as a potential treatment in the occurrence and development of diabetic renal injury