Administration of circRNA_0075932 shRNA exhibits a therapeutic effect on burn-associated infection in obese rats

Abstract

miR-495 and miR-142–3p suppress inflammatory response. Circ_0075932 is overexpressed in the burned skin of obese individuals and is involved in the regulation of PUM2 and AuroraA kinase, thus activating the NF-kB pathway. Obesity significantly influences the length of hospital stay for paediatric burn patients, who present symptoms of slower healing or greater functional impairment. In this study, the relationship between the abovementioned genes was assessed using an obese rat burn model. Luciferase assays, real-time PCR, Western blotting and ELISA assays were performed to explore the regulatory relationships of circRNA_0075932/miR-142, circRNA_0075932/miR-495, miR-142/NLRP3, and miR-495/PUM2. Luciferase assays indicated that miR-142 effectively suppressed the expression of circRNA_0075932/NLRP3 while miR-495 inhibited the expression of circRNA_0075932/PUM2. Downregulation of circRNA_0075932 suppressed the expression of circRNA_0075932/NLRP3/PUM2 and activated the expression of miR-142/miR-495. Exosomes collected from lenti-circRNA_0075932 shRNA-treated ADSCs showed remarkable efficiency in maintaining the post heat stress (PHS)-induced dysregulation of circRNA_0075932, miR-142, miR-495, NLRP3, PUM2, AuroraB, Ika, NF-kB, TNF-α, IL-1β, and MCP-1 in THP-1 cells. Moreover, EXO-Lenti-circRNA_0075932 shRNA significantly restored burn-induced dysregulation of circRNA_0075932, miR-142, miR-495, NLRP3, PUM2, AuroraB, Ika, NF-kB, TNF-α, IL-1β, and MCP-1 in obese rats. In conclusion, this study confirmed that the expression of circ_0075932 in adipose tissue is evidently increased in burn-associated infection in obese rats. Moreover, the administration of circ_0075932 shRNA exhibited a therapeutic effect upon burn-associated infection in obese rats by suppressing the expression of circ_0075932.