Inhibition of lncRNA NEAT1 suppresses the inflammatory response in IBD by modulating the intestinal epithelial barrier and by exosome-mediated polarization of macrophages

Abstract

Inflammatory bowel disease (IBD) is a multifactorial inflammatory disease, and increasing evidence has demonstrated that the mechanism of the pathogenesis of IBD is associated with intestinal epithelial barrier injury. Long non‑coding RNAs (lncRNAs) are a class of transcripts >200 nucleotides in length with limited protein‑coding capability. Nuclear paraspeckle assembly transcript 1 (NEAT1) is a recently identified nuclear‑restricted lncRNA, which localizes in subnuclear structures, termed paraspeckles, and is involved in the immune response in a variety of ways. However, the function of NEAT1 in IBD remains to be fully elucidated. In the present study, reverse transcription‑quantitative polymerase chain reaction assays were performed to determine the expression levels of NEAT1 lncRNA in IBD serum samples and tissues. Furthermore, the effect of NEAT1 on the cell permeability of colon cells was investigated via determination of trans‑epithelial electrical resistance as well as performance of western blot and immunofluorescence assays. In addition, dextran sodium sulfate assays were performed to investigate the effect of downregulation of NEAT1 in IBD of mice. The present study detected the expression levels of NEAT1 in IBD cells and animal models to examine the changes in intestinal epithelial cell permeability following inhibition of the expression of NEAT1. In addition, phenotypic transformation was examined following different treatments in epithelial cells and macrophages. The results suggested that the expression of NEAT1 was high in IBD and was involved in the inflammatory response by regulating the intestinal epithelial barrier and through exosome‑mediated polarization of macrophages. The downregulation of NEAT1 suppressed the inflammatory response by modulating the intestinal epithelial barrier and through exosome‑mediated polarization of macrophages in IBD. The results of the present study revealed a potential strategy of targeting NEAT1 for IBD therapy.

Depression of lncRNA NEAT1 Antagonizes LPS-Evoked Acute Injury and Inflammatory Response in Alveolar Epithelial Cells via HMGB1-RAGE Signaling

“…Intriguingly, NEAT1 has been recently identified as a novel inflammatory regulator in human lupus [24]. Additionally, blocking NEAT1 expression may treat inflammatory bowel disease by suppressing inflammatory progression [25]. The anti-inflammatory efficacy of NEAT1 also has been demonstrated in mice with traumatic brain injury [12].…”

Transcriptome profiling of ulcerative colitis mouse model suggests biomarkers and therapeutic targets for human colitis

“…39 In UC mouse blood lncRNAs Neat1 and Panct2 also showed to be SDE in disease. Neat1 is shown to be pro-inflammatory and its inhibition suppresses the inflammatory response in IBD, 40 whereas little is known about Panct2. Moreover, numerous SDE lncRNAs not reported before in UC mouse including top three upregulated 9130221F21Rik, E230034D01Rik, 1200007C13Rik in colon and Gm7457, Gm37800, Gm32486 in blood and many more up-and downregulated new lncRNAs were identified in our study.…”

Long non-coding RNA NEAT1 inhibits oxidative stress-induced vascular endothelial cell injury by activating the miR-181d-5p/CDKN3 axis

“…Previous reports have shown that NEAT1 participates in several biological events, such as proliferation, polarization invasion and metastasis [31][32][33]. However, the function of NEAT1 in EC dysfunction remains unknown.…”