circFLNA promotes intestinal injury during abdominal sepsis through Fas-mediated apoptosis pathway by sponging miR-766-3p

• Published in: Inflammation research 2023-03, Vol.72 (3), p.509-529
• Main Authors: Ye, Ling, Shi, Yuan, Zhang, Huifeng, Chen, Chao, Niu, Jingjing, Yang, Jianxu, Li, Zhifeng, Shao, Huanzhang, Qin, Bingyu
• Format: Article
• Language: English
• Subjects: Abdomen; Allergology; Animals; Apoptosis; Biomedical and Life Sciences; Biomedicine; Cecum; Communicable Diseases; Dermatology; Epithelial cells; Epithelium; Immunology; In vivo methods and tests; Inflammation; Injuries; Intestinal Perforation; Intestine; Intraabdominal Infections; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Mice; MicroRNAs - genetics; Neurology; Original Research Paper; Perforation; Pharmacology/Toxicology; Rheumatology; RNA, Circular - genetics; Sepsis; Sepsis - genetics; Therapeutic targets; Toxins
• ISSN: 1023-3830; 1420-908X
• DOI: 10.1007/s00011-023-01688-1

Background Intra-abdominal infections are the second most common cause of sepsis in the intensive care unit. Intestinal epithelial injury due to abdominal sepsis results in a variety of pathological changes, such as intestinal bacteria and toxins entering the blood, leading to persistent systemic inflammation and multiple organ dysfunction. The increased apoptosis of intestinal epithelial cells induced by sepsis further exacerbates the progression of sepsis. Although several studies have revealed that circRNAs are involved in intestinal epithelial injury in sepsis, few studies have identified the roles of circRNAs in intestinal epithelial apoptosis. Methods We used laser capture microdissection to obtain purified epithelial cells located in intestinal crypts from four patients with abdominal sepsis induced by intestinal perforation and four samples from age and sex-matched non-septic patients. Microarray analysis of circRNAs was conducted to assess differentially expressed circRNAs between patients with and without sepsis. Lastly, in vitro and in vivo assays were performed to study the mechanism of circFLNA in intestinal epithelial apoptosis during sepsis. Results circFLNA was upregulated in the intestinal epithelium after abdominal sepsis induced by intestinal perforation. Inhibition of miR-766-3p impaired si-circFLNA-mediated inhibition of apoptosis and inflammation factor levels in lipopolysaccharide (LPS)-treated HIEC-6 cells. circFLNA aggravated apoptosis and inflammation through the Fas-mediated apoptosis pathway in both LPS-treated HIEC-6 cells and a mouse cecal ligation and puncture model. Conclusion Our findings showed that circFLNA promotes intestinal injury in abdominal sepsis through the Fas-mediated apoptosis pathway by sponging miR-766-3p. The circFLNA/miR-766-3p/Fas axis has potential as a novel therapeutic target for treating intestinal injury in sepsis.