circVMA21 combining with TAF15 stabilizes SOCS3 mRNA to relieve septic lung injury through regulating NF-κB activation

• Published in: Molecular immunology 2022-11, Vol.151, p.183-192
• Main Authors: Zhu, Zi-Gui, Liao, Gu-Qing, Zhang, Jian-Xin, He, Cheng-Jian, Ni, Zhi-Chao
• Format: Article
• Language: English
• Subjects: circVMA21; Lung injury; NF-κB; Sepsis; SOCS3; TAF15
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/j.molimm.2022.07.004

Lung injury is a severe complication of sepsis, which brings great threats and challenges to human health. CircVMA21 has exhibited powerful anti- inflammation capacity. However, its underlying molecule mechanism remains blurry. Lipopolysaccharide (LPS) was used to treat mice and WI-38 cells to establish models of lung injury caused by sepsis. Lung injury was evaluated using HE staining. Cell apoptosis was tested by TUNEL and flow cytometry. Levels of inflammatory cytokines were detected using ELISA assay. CircVMA21 and SOCS3 expression was measured using RT-qPCR. The ROS, MDA, SOD and GSH production were monitored by commercial kits. The protein expression was examined with western blot. The correlations among circVMA21, SOCS3 and TAF15 were confirmed using RIP and RNA-pull down. The expression of circVMA21 and SOCS3 was downregulated in LPS-induced lung injury of mice and WI-38 cells. Overexpressing circVMA21 or SOCS3 assuaged LPS-induced cell injury through repressing the levels of inflammatory factors, oxidative stress and cell apoptosis. NF-κB signaling pathway was inactivated by circVMA21 or SOCS3 overexpression. circVMA21 enhanced the stabilization of SOCS3 mRNA via interplaying with TAF15. SOCS3 knockdown destroyed the beneficial impacts of circVMA21 overexpression on LPS-induced cell injury. CircVMA21 suppressed LPS-induced the levels of inflammatory factors, oxidative stress and cell apoptosis and improved LPS-induced lung injury by mediating TAF15/SOCS3/NF-κB axis. •circVMA21 and SOCS3 were lowly expressed in lung injury caused by sepsis.•circVMA21 restrained inflammatory response and oxidative stress to relieve cell injury by LPS disposal.•circVMA21 reinforced the stability of SOCS3 mRNA through recruiting TAF15.•SOCS3 relieved cell injury by LPS disposal via inhibiting NF-κB pathway.•circVMA21 alleviated cell injury by LPS disposal through regulating TAF15/SOCS3/NF-κB axis.