RETRACTED: Kcnq1ot1/miR-381-3p/ETS2 Axis Regulates Inflammation in Mouse Models of Acute Respiratory Distress Syndrome

Abstract

Inflammatory mediators play a key role in the pathogenesis of acute respiratory distress syndrome (ARDS). In this study, we aimed to explore the involvement of the Kcnq1 opposite strand/antisense transcript 1 (Kcnq1ot1)/miR-381-3p/E26 transformation-specific proto-oncogene 2 (ETS2) axis in inflammation of lipopolysaccharide (LPS)-induced ARDS. Microarray analysis revealed ETS2 as an upregulated gene in ARDS. Then, a LPS-induced ARDS mouse model was constructed, with a series of gain- or loss-of-function experiments conducted to evaluate the lung function and neutrophil extracellular trap (NET) formation in lung tissue and determine the neutrophil number, myeloperoxidase (MPO) activity, and inflammatory factor levels in bronchoalveolar lavage fluid (BALF). As the results revealed, downregulated expression of ETS2 resulted in improved lung function, decreased NETs, MPO activity, and levels of interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α), as well as increased IL-10 level. Then, the assays of dual-luciferase reporter, RNA-binding protein immunoprecipitation (RIP), and RNA pull-down were performed to validate that Kcnq1ot1 promoted ETS2 expression by competitively binding to miR-381-3p. Meanwhile, it was also found that Kcnq1ot1 silencing reversed the promotive effect of EST2 on ARDS. Our results provide evidence that Kcnq1ot1 silencing may reduce the inflammatory response in LPS-induced ARDS via inhibition of miR-381-30-dependent ETS2, thereby presenting new molecular understanding for the development of ARDS.

Upregulation of matrix metalloproteinase 9 (MMP9)/tissue inhibitor of metalloproteinase 1 (TIMP1) and MMP2/TIMP2 ratios may be involved in lipopolysaccharide-induced acute lung injury

“…L2880; Sigma-Aldrich, St. Louis, MO, USA). 18,19 The NC group was injected with the same amount of saline. The two groups were further divided into subgroups of 2, 6, 12, and 24 hours with six rats for each time point.…”

SNHG15 knockdown inhibits diabetic nephropathy progression in pediatric patients by regulating the miR-141/ICAM-1 axisin vitro

“…Because the molecular mechanism is complex in cell processes, the effect of SNHG15 may be influenced by other regulatory factors, especially for the adverse changes. Numerous studies have been revealed that miRNAs serve as suppressors in the levels of inflammatory factors of multiple diseases [ 35–38 ], including in DN in vitro [ 20–22 ]. Zha et al have demonstrated that the decreased expression of miR-181a dramatically elevates the levels of inflammatory factors in HG-treated RAW264.7 cells, while the expression of inflammatory factors is inhibited by miR-181a overexpression [ 20 ].…”

“…Numerous studies have been revealed that miRNAs serve as suppressors in the levels of inflammatory factors of multiple diseases [35][36][37][38], including in DN in vitro [20][21][22]. ICAM-1 has been confirmed to distinctly up-regulate in DN in vitro [42][43][44][45].…”

CircHIPK3/miR-381-3p axis modulates proliferation, migration, and glycolysis of lung cancer cells by regulating the AKT/mTOR signaling pathway

“…The tumor suppressor role of miR-381-3p has been demonstrated, including inhibiting cell proliferation, metastasis, and facilitating cell cycle arrest and apoptosis [ 16 , 18 ]. In addition, miR-381-3p had a connection with inflammatory responses in mouse models of spinal cord injury and acute respiratory distress syndrome [ 28 , 29 ]. In NSCLC, miR-381-3p was sponged by circFGFR1, an oncogenic circRNA functioning in proliferation, metastasis, and immune evasion capacities of tumor cells [ 19 ].…”