Asprosin Promotes Human Renal Tubular Epithelial Cells Apoptosis by Inhibiting Autophagy

Asprosin, a recently discovered adipokine, is a glucotropic hormone involved in the pathogenesis of diabetes and closely associated with diabetic kidney disease (DKD). Renal tubular epithelial cell injury is one of the important pathological characteristic of DKD. However, the precise molecular mechanism remains unclear. In this study, we validated the role of Asprosin in proximal tubular epithelial cells injury in DKD. The expression level of Asprosin was found to be higher in kidney tissues and plasma of DKD patients than in the healthy group. Additionally, the kidney tissues of DKD mouse and HK-2 cells treated with high glucose showed elevated Asprosin expression. Moreover, Asprosin intervention in HK-2 cells led to insufficient autophagy and increased apoptosis. These findings suggest that Asprosin exacerbates autophagy disturbance and induces apoptosis in HK-2 cells under high glucose conditions, and our further studies verified that Asprosin promotes HK-2 cell apoptosis by inhibiting autophagy. Thus, our findings demonstrate for the first time that elevated glucose levels can upregulate Asprosin in both kidney tissue and plasma. Moreover, Asprosin can enhance apoptosis in HK-2 cells by inhibiting autophagy, aggravate autophagy dysregulation and apoptosis caused by high glucose, and promote injury in renal tubular epithelial cells.