Podocyte protection by Angptl3 knockout via inhibiting ROS/GRP78 pathway in LPS-induced acute kidney injury.

Acute kidney injury (AKI) caused by sepsis has a high incidence and poor prognosis. Thus, novel strategies that minimize AKI are urgently needed. In our previous research, we found that angiopoietin-like protein 3 (Angptl3) knockout exerts protective effects on kidney injury in adriamycin nephropathy. However, the role of Angptl3 in the pathogenesis of AKI is largely unclear. This study aimed to explore the renal protective effects and molecular mechanisms of Angptl3 knockout in lipopolysaccharide (LPS)-induced AKI in mice. B6;129S5 mice were injected intraperitoneally with 10 mg/kg of LPS to induce AKI. Then, the changes in renal function, podocyte apoptosis, inflammatory factors (tumor necrosis factor-α, TNF-α; interleukin-6, IL-6; and interleukin-1β, IL-1β), reactive oxygen species (ROS), and endoplasmic reticulum (ER) stress were measured. The mechanism of Angptl3 in the apoptosis of podocytes was also investigated. Results showed that Angptl3 knockout significantly alleviated the renal dysfunction and apoptosis of podocytes induced by LPS. Angptl3 knockout was associated with the (1) downregulation of Bax and upregulation of Bcl-2; (2) amelioration of the abnormal expression of nephrin, podocin, and CD2AP; (3) reduced ER stress; (4) reduced secretions of TNF-α, IL-6, and IL-1β; and (5) regulation of Bax expression via the ROS-related ER stress pathway. Our findings revealed that Angptl3 knockout alleviated the apoptosis of podocytes by regulating the ROS/GRP78 signaling pathway.