Trigonelline regulates Wnt/β-catenin signaling in glomerular mesangial cells under high glucose conditions

Abstract

Background: Trigonelline have hypoglycemic effects. In previous animal experiments, we observed that trigonelline (TRL) treat-ment attenuated metabolic abnormalities associated with hyperglycemic conditions in the experimental DN model. In streptozotocin (STZ)-induced rats, TRL treatment reduced albuminuria, lowered blood sugar, improved renal function and alleviated the pathological alterations within the glomerulus. Methods: We stimulated human mesangial cells (HMC) with high glucose (30 mmol / L) medium. HMCs were transfected with β-catenin plasmid or siRNA to investigate the effect of trigonelline on high glucose-induced excessive proliferation and apoptosis of HMCs, and to understand its mechanism of action. Cell viability was measured by MTT assay. Flow cytometry was used to detect the cell cycle. Cell apoptosis was evaluated by flow cytometry and terminal dUTP transferase nick end labeling (TUNEL) assay. Protein and mRNA expression of β-catenin, Wnt5a, TCF4, Cyclin D1, and CDK4 were detected by western blotting and RT-PCR, respectively. Results: Trigonelline inhibited cell proliferation by blocking cell-cycle progression at the G1 phase and decreased apoptosis via the Wnt/β-catenin pathway. Elevated glucose levels enhanced the expression of β-catenin, an important modulator of diabetic nephropathy, while trigonelline restored up-regulation. Conclusions: High glucose and high expression of β-catenin could lead to cell injury; however, this effect was mitigated by trigonelline via managing the canonical Wnt/β-catenin signaling pathway.