Changes and significance of SIRT3 expression in cellular transdifferentiation induced by uric acid

Abstract:

Objective：To explore the role of the silent information regulator 3（SIRT3） in the transdifferentiation process of mouse’s glomerular mesangial cells（MC53） caused by high levels of uric acid. Methods：The MC53 cells were cultured in media containing different concentrations of uric acid（0.05，0.1，0.3 mmol/L） for 48 h. The intracellular reactive oxygen species（ROS） level was deter－mined with fluorescence microscope and flow cytometry. The mRNA and protein expression levels of SIRT3，α-smooth muscle actin （α-SMA），transforming growth factor-β1（TGF-β1），fibronectin（FN） were evaluated through real-time PCR and Western blot. The effect of SIRT3 on oxidative stress and cell transdifferentiation was assessed by transfection of siSIRT3 into MC53 cells. Results：UA increased ROS production in a concentration-dependent manner with a maximal stimulation at 0.3 mmol/L. UA stimulated the down regulation of SIRT3 and upregulation of the α-SMA，TGF-β1 and FN mRNA and proteins in a concentration manner. The ROS level and the expression of α-SMA，TGF-β1，FN proteins were elevated in cells transfected with siSIRT3 after incubation with uric acid. Conclusion：High concentration of uric acid can induce MC53 cells transdifferentiation，SIRT3 may play an important role in cell trans－differentiation.