PMID- 33202146 OWN - NLM STAT- MEDLINE DCOM- 20210222 LR - 20210222 IS - 1535-4989 (Electronic) IS - 1044-1549 (Print) IS - 1044-1549 (Linking) VI - 64 IP - 2 DP - 2021 Feb TI - MicroRNA-574-5p Attenuates Acute Respiratory Distress Syndrome by Targeting HMGB1. PG - 196-207 LID - 10.1165/rcmb.2020-0112OC [doi] AB - Acute respiratory distress syndrome (ARDS) is a critical condition with high mortality. HMGB1 (high-mobility group protein B1) is one of the key proinflammatory factors in the ARDS "inflammatory storm." According to previous studies, some microRNAs (miRNAs) play important roles in this process. We aimed to determine the contributing miRNAs targeting the expression and release of HMGB1. miRNA expression in the peripheral blood of patients with ARDS was measured by miRNA microarray. miRNAs targeting HMGB1 were screened and explored for further study. In LPS-induced cell and mouse ARDS models, we explored the effect of this miRNA on the expression and secretion of HMGB1 by Western blot, real-time qPCR, and ELISA. The effects of this miRNA on the NF-kappaB signaling pathway, proinflammatory cytokines, and NLRP3 (nod-like receptor protein 3) inflammasome were detected by Western blot and real-time qPCR. In ARDS models, microRNA-574-5p (miR-574-5p) expression could be induced by the TLR4/NF-kappaB pathway upon LPS stimulation. It could suppress the inflammatory response by targeting HMGB1. Enforcing the expression of miR-574-5p or HMGB1 siRNA silencing inhibits the activation of NF-kappaB signaling pathway and the NLRP3 inflammasome. Moreover, overexpression of HMGB1 reversed the antiinflammatory effect of miR-574-5p. In ARDS mice, overexpression of miR-574-5p suppresses alveolar leukocytes infiltration, interstitial edema, protein effusion, and inflammation. This study demonstrated that miR-574-5p provided negative feedback to LPS-induced inflammation and relieved ARDS. It may provide new therapeutic strategies for ARDS. FAU - He, Binchan AU - He B AD - Department of Respiratory and Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, China. AD - The Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China; and. FAU - Zhou, Wei AU - Zhou W AD - Department of Respiratory and Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, China. FAU - Rui, Yuwen AU - Rui Y AD - Department of Respiratory and Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, China. FAU - Liu, Lulu AU - Liu L AD - Department of Respiratory and Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, China. FAU - Chen, Bilin AU - Chen B AD - Department of Respiratory and Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, China. FAU - Su, Xin AU - Su X AD - Department of Respiratory and Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, China. AD - Department of Respiratory and Critical Care Medicine, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Respir Cell Mol Biol JT - American journal of respiratory cell and molecular biology JID - 8917225 RN - 0 (Cytokines) RN - 0 (HMGB1 Protein) RN - 0 (HMGB1 protein, mouse) RN - 0 (Inflammasomes) RN - 0 (Lipopolysaccharides) RN - 0 (MIRN574 microRNA, mouse) RN - 0 (MicroRNAs) RN - 0 (NF-kappa B) SB - IM CIN - Am J Respir Cell Mol Biol. 2021 Feb;64(2):158-160. PMID: 33522886 MH - Animals MH - Cells, Cultured MH - Cytokines/metabolism MH - Endothelial Cells/metabolism MH - HMGB1 Protein/*metabolism MH - Humans MH - Inflammasomes/metabolism MH - Inflammation/metabolism MH - Lipopolysaccharides/pharmacology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - MicroRNAs/*metabolism MH - NF-kappa B/metabolism MH - Respiratory Distress Syndrome/*metabolism MH - Signal Transduction/physiology PMC - PMC7874400 OTO - NOTNLM OT - HMGB1 OT - NF-kappaB OT - NLRP3 inflammasome OT - miR-574-5p EDAT- 2020/11/18 06:00 MHDA- 2021/02/23 06:00 PMCR- 2021/02/01 CRDT- 2020/11/17 20:05 PHST- 2020/11/18 06:00 [pubmed] PHST- 2021/02/23 06:00 [medline] PHST- 2020/11/17 20:05 [entrez] PHST- 2021/02/01 00:00 [pmc-release] AID - 10.1165/rcmb.2020-0112OC [doi] PST - ppublish SO - Am J Respir Cell Mol Biol. 2021 Feb;64(2):196-207. doi: 10.1165/rcmb.2020-0112OC.