Aims: Apoptosis of podocytes plays a crucial role in diabetic nephropathy (DN) development, and astragaloside (AS-IV) has a significant impact on podocyte apoptosis. This study aims to explore the effect of AS-IV on diabetic nephropathy progression.
Materials and methods: The diabetic nephropathy model was established in rats with streptozotocin (STZ) injection. The albuminuria was examined by using the enzyme linked immunosorbent assay (ELISA). The expression of miR-378, tumor-necrosis factor (TNF) receptor (TNFR)-associated factor 5 (TRAF5) mRNA and protein was analyzed by qRT-PCR and western blot, respectively. Cell transfection was conducted for modulating endogenous expression of miR-378. Dual luciferase reporter assay was used to evaluate the interaction between miR-378 and TRAF5. The terminal deoxynucleotidy transferase dUTP nick end labeling (TUNEL) staining assay was performed for apoptosis detection.
Key findings: AS-IV protected diabetic rats from developing into diabetic nephropathy. The expression of miR-378 was down-regulated in diabetic nephropathy rats, which was reversed by AS-IV. AS-IV enhanced the expression of miR-378 in podocytes treated with high glucose. MiR-378 negatively regulated TRAF5. AS-IV inhibited the expression of TRAF5 through miR-378. AS-IV suppressed apoptosis of podocytes via targeting miR-378.
Significance: AS-IV suppresses apoptosis of the podocytes through the miR-378/TRAF5 signaling pathway, and thereby repressing diabetic nephropathy development.
Keywords: AS-IV; Diabetic nephropathy; Podocytes; TRAF5; miR-378.
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