CCL25 Stabilized by IGF2BP3 Induces Cellular Oxidative Stress to Promote Septic Lung Injury

Septic lung injury is a severe clinical problem with high mortality, and oxidative stress plays a critical role in its pathogenesis. This research focused on investigating how IGF2BP3 stabilizes CCL25 mRNA and its subsequent effects on cellular oxidative stress and septic lung injury. An in vitro cell injury model was established using LPS. The CCK-8 assay, flow cytometry and ELISA were employed to evaluate cell viability, death and inflammatory cytokine levels respectively. ROS accumulation, MDA content and antioxidant enzyme activities (SOD and GSH-Px) were quantified. Analysis of IGF2BP3 and CCL25 expression was conducted through qPCR and Western Blot. To confirm the interaction between IGF2BP3 and CCL25 mRNA, RIP and RNA pull-down were conducted. CCL25 mRNA stability was assessed following actinomycin D administration. Sepsis-caused lung injury model was created using CLP in mice. Further validation of CCL25's involvement in septic lung injury was conducted through qPCR, Western Blot, HE, ELISA and measurement of oxidative stress indicators. After LPS treatment, the cell viability was significantly decreased and the cell death, inflammation as well as oxidative stress were induced, the expressions of IGF2BP3 as well as CCL25 were markedly increased. Knockdown of CCL25 alleviated cellular oxidative stress and cellular damage caused by LPS. In addition, IGF2BP3 bound CCL25 and stabilized CCL25 mRNA, thus regulating LPS-induced cellular oxidative stress and cellular damage. In vivo, knockdown of CCL25 alleviated oxidative stress and inflammatory injury of lung tissue. CCL25 stabilized by IGF2BP3 could promote septic lung injury by inducing cellular oxidative stress.