Research Paper Volume 14, Issue 12 pp 5059—5074
The circular RNA hsa_circ_0003091 regulates sepsis-induced lung injury by sponging the miR-149/Smad2 axis
- 1 Emergency Department, China-Japan Friendship Hospital, Beijing 100029, China
- 2 Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China
- 3 Department of Respiratory and Critical Care Medicine, China-Japan Friendship Hospital, Beijing 100029, China
- 4 Surgical Intensive Care Unit (SICU), China-Japan Friendship Hospital, Beijing 100029, China
- 5 Department of Digestive, Beijing Ditan Hospital Capital Medical University, Beijing 100015, China
- 6 Department of Emergency, Peking University People's Hospital (PKUPH), Beijing 100044, China
Received: December 1, 2021 Accepted: May 30, 2022 Published: June 14, 2022
https://doi.org/10.18632/aging.204125How to Cite
Copyright: © 2022 Shen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Sepsis-induced acute lung injury (ALI) is a severe cause of death. Increasing evidence has identified circular RNAs (circRNAs) acting as critical regulators of human diseases. However, their expression pattern and underlying mechanisms in ALI remain unclear. Herein, we screened the circRNAs of ALI patients and constructed a lung injury murine model using lipopolysaccharides (LPS) induction. Functional analyses of targeted circRNA were performed in vivo and in vitro. Then, the downstream miRNA and mRNA of specific circRNAs were identified. Compared to healthy subjects, 35 circRNAs were upregulated and 9 circRNAs were downregulated in sepsis patients. The top 10 differentially expressed circRNAs were selected for validation and has_circ_0003091 was selected. The ALI mice presented significantly elevated has_circ_0003091 (mmu_circ_0015268). The functional analysis revealed that mmu_circ_0015268 contributed to the pulmonary injury, cell apoptosis, inflammatory responses, and endothelial activation in the ALI murine model. On the other hand, silencing mmu_circ_0015268 showed protective effects in LPS-treated mice and PMVECs. Furthermore, mmu_circ_0015268 sponged miR-149 to upregulate the expression of its target Smad2. In summary, we demonstrated that has_circ_0003091 might be a novel target for the management and treatment of sepsis-induced ALI.