Asprosin Promotes High Glucose-Induced Apoptosis of Human Renal Tubular Epithelial Cells by Inhibiting Autophagy

Background 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 characteristics of DKD. However, the precise molecular mechanism remains unclear. In this study, we aimed to investigate the role of Asprosin in proximal tubular epithelial cells injury in DKD. Methods The plasma Asprosin level was measured using ELISA in both healthy people and patients with DKD. Immunohistochemistry was employed to detect the level of Asprosin in renal biopsy tissues from DKD patients as well as normal renal tissues adjacent to cancer resected by surgery. Western Blot and q-PCR were utilized to determine the level of Asprosin in DKD mouse kidney tissues. HK-2 cells were exposed to high glucose conditions to simulate injury in renal tubular epithelial cells seen in DKD patients. Following intervention with Asprosin, we analyzed the expression of HK-2 gene, autophagic flux and apoptosis. Results The expression level of Asprosin was found to be higher in kidney tissues and plasma from DKD patients compared to the control group. In addition, the kidney tissues of DKD mice and HK-2 cells treated with high glucose exhibited elevated levels of Asprosin expression. Furthermore, intervention with Asprosin in HK-2 cells resulted in insufficient autophagy and increased apoptosis. These findings suggest that Asprosin exacerbates disturbance in autophagy and induces apoptosis in HK-2 cells under the high glucose conditions. Importantly, our results indicate that Asprosin promotes the apoptosis of HK-2 cells by inhibiting autophagy. Conclusions Our findings collectively demonstrate that elevated glucose levels can induce the upregulation of Asprosin in both kidney tissue and plasma. Furthermore, Asprosin has the ability to enhance apoptosis in HK-2 cells by inhibiting autophagy, exacerbate autophagy dysregulation and apoptosis caused by high glucose, as well as promote injury in renal tubular epithelial cells.