SOX4 silencing alleviates renal injury in rats with acute renal failure by inhibiting the NF-κB signaling pathway and reducing apoptosis and oxidative stress

Acute renal failure (ARF) is a huge threat to the lives of most patients in intensive care units, and there is currently no satisfactory treatment strategy. SRY-box transcription factor 4 (SOX4) plays a key role in the development of various diseases, but its effect on ARF is unknown. Therefore, this study aimed to explore the relationship between SOX4 and ARF. Blood samples were collected from 20 ARF patients and 20 healthy volunteers. We also established an ARF rat model by excising the right kidney and ligating the left renal artery, and SOX4 knockdown in ARF rats was achieved down by means of lentiviral Infection. Subsequently, we used quantitative polymerase chain reaction and western bolt assays to detect the expression levels of SOX4 and nuclear factor-κB (NF-κB) signaling pathway-related proteins in human blood or rat renal tissue and hematoxylin and eosin and terminal deoxynucleotidyl transferase (TdT) 2'-deoxyuridine 5'-triphosphate (dUTP) nick-end labeling staining to observe the pathological changes and Apoptosis of renal tissue. Enzyme-linked immunosorbent assay and biochemical kits were used to measure the levels of renal function-related Indicators (blood urea nitrogen, creatinine, and neutrophil gelatinase-associated lipocalin) and inflammatory factors (interleukin [IL]-1β, IL-6, and tumor necrosis factor-alpha), as well as changes in oxidative stress-related Indicators (malondialdehyde [MDA], superoxide dismutase [SOD], and Reactive Oxygen Species [ROS]) in rat serum. SOX4 expression levels in blood samples from ARF patients and renal tissue from ARF rats were significantly higher compared with those in healthy volunteers and control rats, respectively. ARF model rats displayed the typical ARF phenotype, while SOX4 silencing significantly improved pathological injury and Apoptosis of renal tissue in ARF rats. Moreover, SOX4 silencing significantly inhibited increased levels of renal function-related Indicators and inflammatory factors and reduced the level of excessive oxidative stress (MDA and ROS were upregulated, and SOD was downregulated) in ARF rats. SOX4 also reduced the activity of the NF-κB signaling pathway in ARF samples. Thus, SOX4 knockdown may reduce oxidative stress, the inflammatory response, and Apoptosis by reducing the activity of the NF-κB signaling pathway, thereby improving renal injury in ARF rats.

NF‐κB signaling pathway; SRY‐box transcription factor 4 (SOX4); acute renal failure (ARF); oxidative stress; renal function.