PMID- 35722395 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220830 IS - 2305-5839 (Print) IS - 2305-5847 (Electronic) IS - 2305-5839 (Linking) VI - 10 IP - 10 DP - 2022 May TI - Deletion of the miR-144/451 cluster aggravates lethal sepsis-induced lung epithelial oxidative stress and apoptosis. PG - 538 LID - 10.21037/atm-22-1024 [doi] LID - 538 AB - BACKGROUND: Sepsis is associated with a high mortality rate. A major cause of death in sepsis patients is respiratory failure, which is characterized by oxidative injury, epithelial apoptosis, and increased lung permeability. MicroRNAs (miRs) are important regulators of sepsis progression. METHODS: This study aimed to explore the role of miR-144/451 in sepsis in mice. Experimental sepsis was induced in C57BL/6 mice by cecal ligation and puncture (CLP). RESULTS: CLP significantly induced systemic inflammation, lung permeability, and lung epithelial apoptosis with downregulated messenger RNA (mRNA) levels of antioxidant enzymes. The miR-144/451 knockout mice had a lower 48-hour survival rate, higher plasma tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) levels, and greater pulmonary permeability compared with wild-type mice after CLP. CLP also markedly increased interstitial hemorrhage, collapsed more alveolar sacs, and increased the number of terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive and Bcl-2-associated X (Bax)-positive cells in miR-144/451 knockout lung tissues, with elevated mRNA levels of Bax and reduced activities of catalase (Cat), glutathione peroxidase 1(Gpx1). MiR-451 negatively regulated 14-3-3zeta expression evidenced in miR-144/451 knockout lungs and the A549 cell line. In lipopolysaccharide (LPS)-induced A549 cells, miR-451 overexpression remarkably suppressed the production of reactive oxygen species, inhibited cell apoptosis, and enhanced levels of FoxO3 protein and related enzymes. CONCLUSIONS: Deletion of the miR-144/451 cluster aggravated sepsis-induced oxidative injury of lung epithelial cells. CI - 2022 Annals of Translational Medicine. All rights reserved. FAU - Wu, Fan AU - Wu F AD - Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China. AD - Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research, Yangzhou, China. FAU - Yuan, Xiaoling AU - Yuan X AD - Children Rehabilitation Department, Yangzhou Maternal and Child Health Hospital, Yangzhou, China. FAU - Liu, Weili AU - Liu W AD - Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China. AD - Intensive Care Unit, Affiliated Hospital of Yangzhou University, Yangzhou, China. FAU - Meng, Lijun AU - Meng L AD - Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China. AD - Intensive Care Unit, Affiliated Hospital of Yangzhou University, Yangzhou, China. FAU - Li, Xiuru AU - Li X AD - Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China. FAU - Gao, Xiang AU - Gao X AD - Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China. FAU - Zhou, Shuting AU - Zhou S AD - Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China. AD - Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research, Yangzhou, China. FAU - Fang, Lei AU - Fang L AD - Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China. AD - Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research, Yangzhou, China. FAU - Yu, Duonan AU - Yu D AD - Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China. AD - Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research, Yangzhou, China. AD - Intensive Care Unit, Affiliated Hospital of Yangzhou University, Yangzhou, China. LA - eng PT - Journal Article PL - China TA - Ann Transl Med JT - Annals of translational medicine JID - 101617978 PMC - PMC9201188 OTO - NOTNLM OT - apoptosis OT - epithelial OT - miR-144/451 OT - oxidative stress OT - sepsis COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-1024/coif). The authors have no conflicts of interest to declare. EDAT- 2022/06/21 06:00 MHDA- 2022/06/21 06:01 PMCR- 2022/05/01 CRDT- 2022/06/20 04:07 PHST- 2022/01/25 00:00 [received] PHST- 2022/05/17 00:00 [accepted] PHST- 2022/06/20 04:07 [entrez] PHST- 2022/06/21 06:00 [pubmed] PHST- 2022/06/21 06:01 [medline] PHST- 2022/05/01 00:00 [pmc-release] AID - atm-10-10-538 [pii] AID - 10.21037/atm-22-1024 [doi] PST - ppublish SO - Ann Transl Med. 2022 May;10(10):538. doi: 10.21037/atm-22-1024.