Molecular mechanism of miRNA-23a in sepsis-induced lung injury.

MicroRNA-23a-3p (miR-23a) is a novel gene regulator involved in inflammation. This study aimed to explore the molecular mechanism of miR-23a in sepsis-induced lung injury both in vitro and in vivo. Lipopolysaccharide (LPS)- and ATP-stimulated human myeloid leukemia mononuclear cells (THP-1) and Human Bronchial Epithelial Cells (BEAS-2B) cell lines were used, while cecal ligation and puncture (CLP)-induced sepsis BABL/c mice were constructed. The mRNA expression levels of interleukin (IL)-18, IL-1β, and miR-23a were determined, and Western blotting was used to measure CXCR4/PTEN/PI3K/AKT signaling. The concentrations of cytokines and Nod-like receptor family pyrin domain-containing 3 (NLRP3) were determined using an enzyme-linked immunosorbent assay. Lung tissue of mice was subjected to hematoxylin-eosin staining for examining myocardial injury. MiR-23a inhibited NLRP3 inflammasome activation in LPS- and ATP-stimulated THP-1 and BEAS-2B cells (P<0.05). Overexpression of miR-23a decreased the lactate dehydrogenase release rate in the cells (P<0.05). Meanwhile, miR-23a overexpression decreased the concentration and gene expression of IL-1β and IL-18 in CXCR4 positive cells (P<0.05). Conversely, miR-23a knockdown increased the concentration and gene expression of IL-1β and IL-18 (P<0.05). Additionally, PTEN and p53 proteins were up-regulated in miR-23a mimic group and down-regulated in miR-23a inhibitor group (P<0.05). Furthermore, miR-23a expression was decreased in sepsis-induced lung injury mice (P<0.05). MiR-23a overexpression reduced the sepsis-induced lung injury probably by inhibiting acetylcholinesterase activity and expression levels of IL-1β, IL-18, capase-1, and NLRP3 (P<0.05). miR-23a can significantly alleviate sepsis-induced lung injury in CLP-induced septic mice and LPS-stimulated cell lines by suppressing NLRP3 inflammasome activation and inflammatory response, while promoting the CXCR4/PTEN/PI3K/AKT pathway. AJTR Copyright © 2023.

Citation

Pingli Zhang, Qikun Huang, Peiyuan Liao, Shijing Sun, Jing Yang. Molecular mechanism of miRNA-23a in sepsis-induced lung injury. American journal of translational research. 2023;15(6):3900-3911

PMID: 37434814

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