Deregulated RNAs involved in sympathetic regulation of sepsis-induced acute lung injury based on whole transcriptome sequencing

• Published in: BMC genomics Vol. 23; no. 1; pp. 836 - 17
• Main Authors: Zhang, Jia, Zhang, Zhao, Nie, Xinran, Liu, Yingli, Qi, Yong, Wang, Jing
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 16.12.2022; BioMed Central; BMC
• Subjects: 6-Hydroxydopamine; Acute lung injury; Acute Lung Injury - chemically induced; Acute Lung Injury - genetics; Acute respiratory distress syndrome; Animals; Antibodies; B-cell receptor; Complications and side effects; Cytokines; Denervation; Deregulation; Development and progression; DNA sequencing; Enzyme-linked immunosorbent assay; Exome Sequencing; Gene expression; Gene sequencing; Genetic aspects; Genomics; Health aspects; Immunodeficiency; Inflammation; Injuries; Interleukin 17; Intubation; Laboratories; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Lung - metabolism; Lungs; Lymphocytes B; Medical research; Medicine, Experimental; Membranes; Mice; MicroRNAs; MicroRNAs - genetics; miRNA; ncRNAs; Nerves; Nervous system, Sympathetic; Neural transmission; NF- κB; NF-kappa B - genetics; NF-κB protein; Non-coding RNA; Norepinephrine; Nucleotide sequencing; Physiological aspects; Primary immunodeficiencies; Proteins; Receptors; Regulation; RNA; RNA, Circular - genetics; RNA, Circular - metabolism; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; RNA, Messenger - genetics; Sepsis; Sepsis - complications; Sepsis - genetics; Signal transduction; Signaling; Sympathetic nerve; Sympathetic nerves; Trachea; Transcriptomes; Tumor necrosis factor; Tumor necrosis factor-TNF; Western blotting; China; Beijing China; California; United States > US; Sympathetic nerve; Acute lung injury; Sepsis; NF- κB; ncRNAs
• ISSN: 1471-2164; 1471-2164
• DOI: 10.1186/s12864-022-09073-8

Sympathetic nerves play essential roles in the regulation of lung inflammation, and we investigated the effect of sympathetic denervation (SD) on sepsis-induced acute lung injury (ALI) in mice. Mice were randomized to the control, SD, ALI and SD + ALI, groups. SD and ALI were established through intratracheal 6-hydroxydopamine and intraperitoneal lipopolysaccharide, respectively. Models and gene expressions levels were evaluated by HE staining, ELISA, Western blotting and RT-qPCR. RNA extraction, whole transcriptome sequencing and subsequent biostatistical analysis were performed. Sympathetic denervation in the lungs significantly attenuated lung TNF-ɑ and norepinephrine expression, alleviated sepsis-induced acute lung injury and inhibited NF-κB signaling. Compared with the ALI group, the SD + ALI group exhibited 629 DE circRNAs, 269 DE lncRNAs,7 DE miRNAs and 186 DE mRNAs, respectively. Some DE RNAs were validated by RT-qPCR. CircRNA-miRNA-mRNA regulatory networks in the SD + ALI group revealed enrichment of the B-cell receptor signaling pathway, IL-17 signaling pathway, neuroactive ligand-receptor interaction, CAM, primary immunodeficiency, and cytokine-cytokine receptor interaction terms. The lncRNA-miRNA-mRNA network also revealed inflammation-related signaling pathways. Taken together, based on the successfully established models of SD and ALI, we show here that sympathetic nerves may regulate sepsis-induced ALI supposedly by affecting the expression of circRNAs, lncRNAs, miRNAs, and mRNAs in the lungs. These results may allow for further exploration of the roles of pulmonary sympathetic nerves in sepsis-induced ALI.