ANGPTL4 Improves Mitochondrial Function and Protects Against Acute Kidney Injury

Abstract

Background: Acute kidney injury (AKI) often leads to impaired filtration and excretion of waste products. It is characterized by mitochondrial dysfunction, elevated inflammatory response, and oxidative stress. However, angiopoietin-like 4 (ANGPTL4) plays a significant role in angiogenesis and lipid metabolism, thereby regulating inflammation and protecting cells from injuries. Therefore, this study explored whether ANGPTL4 played roles in protecting against AKI as well as the underlying mechanisms. Methods: The lipopolysaccharide (LPS) was used for stimulating the human renal cortex proximal tubule epithelial HK-2 cells to establish the model of AKI. The changes of ANGPTL4 in LPS-treated HK-2 cells were detected by western blot. Subsequently, small interference (si)RNA/plasmid transfection technology was used to decrease or increase the ANGPTL4 expression. The transfection efficiency was verified using real-time reverse transcriptase-polymerase chain reaction (RT-qPCR). Moreover, the impact of ANGPTL4 on LPS-induced cytotoxicity was determined by measuring cell viability and apoptosis rate using cell counting kit-8 (CCK-8) assay and terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) assay, respectively. Additionally, the levels of LPS-induced cytokines tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) along with changes in cellular reactive oxygen species (ROS) levels were investigated. Finally, the effect of ANGPTL4 on mitochondrial dysfunction and oxidative stress was assessed using mitochondrial function assay kit and ROS detection kit. Results: The level of ANGPTL4 in HK-2 cells decreased after LPS treatment (p < 0.05). Moreover, ANGPTL4 overexpression alleviated LPS-induced cytotoxicity and cell apoptosis (p < 0.01), inhibited the production of LPS-induced cytokines (p < 0.01), and reduced the cellular ROS levels (p < 0.05). Concurrently, ANGPTL4 overexpression improved LPS-induced mitochondrial dysfunction (p < 0.05). Conclusion: In summary, ANGPTL4 can improve mitochondrial dysfunction in LPS-induced AKI and reduce inflammation and oxidative stress. This study offers a new direction for understanding and treating AKI, providing evidence for using ANGTL4 as a novel therapeutic strategy with potential clinical applications.