MicroRNA-223 targets NLRP3 to relieve inflammation and alleviate spinal cord injury

Zhang, Meng; Wang, Lin; Huang, Sihua; He, Xijing

doi:10.1016/j.lfs.2020.117796

Cited by 29 publications

(14 citation statements)

References 37 publications

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“…This was consistent with our findings, in which miRNA-223 expression was significantly decreased following AA-induction of UC in rats. Several studies conducted on different types of inflammatory disease confirmed that the upregulation of miRNA-223 resulted in the inhibition of NLRP3 and consequent inhibition of the inflammatory cytokines IL-1β and IL-18 (Din et al, 2020, Jimenez Calvente et al, 2020, Wu et al, 2020, Zhang et al, 2020), which encouraged us for the first time to investigate the impact of miRNA-223 on the inflammatory response in AA-induced UC. Herein, the pre-treatment with MFE markedly increased the relative expression of miRNA-223, resulting in a marked reduction in the NLRP3 in addition to the inhibition of caspase-1, IL-1β and IL-18 as discussed above.…”

Section: Discussionmentioning

confidence: 95%

Protective effect ofMorus macrouraMiq. fruit extract against acetic acid-induced ulcerative colitis in rats: Involvement of miRNA-223 and TNFα/NFκB/NLRP3 inflammatory pathway

Salama

Darwish

Shaffei

et al. 2020

Preprint

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Tumor necrosis factor receptor (TNFR) activation and nuclear factor kappa B (NFκB) expression play a significant role in the activation of nod-like receptor pyrin domain-1 containing 3 (NLRP3) inflammasome inflammatory pathway, which is involved in the pathogenesis of ulcerative colitis (UC). Furthermore, miRNA-223 expression was shown to exert counter-regulatory effect on NLRP3 expression. Interestingly, polyphenols are attaining increased importance for their potential effectiveness in ameliorating certain diseases owing to their antioxidant and anti-inflammatory activity. In accord, our study attempted to investigate the effect of mulberry tree (Morus macroura) fruit extract (MFE) against acetic acid (AA)- induced UC in rats, which is not previously investigated, based on previous promising results for MFE in alleviating gastric ulcer in rats. First, total phenolic (TPC), total flavonoid (TFC), and total anthocyanin content (TAC) were determined in MFE. Then, MFE (300 mg/kg) and sulfasalazine (Sulfa), as a standard treatment (100 mg/kg), were given orally for seven days before intra-rectal induction of UC by AA (2 ml, 4% v/v) on day eight. The extent of UC was evaluated macroscopically and microscopically. Biochemically, the colonic TNFR1, NLRP3, p- NFκB p65, TNFα, interleukin-1 beta (IL-1β), IL-18 levels, miRNA-223 expression and caspase-1 activity were assayed. MFE significantly reduced macroscopic and microscopic scores, colonic levels of TNFR1, NLRP3, p-NFκB p65, TNFα, IL-1β, IL-18, and caspase-1 activity, and showed increased miRNA-223 expression, almost similarly to Sulfa effects. In conclusion, our study provided a novel impact for MFE against AA-induced UC in rats through affecting miRNA-223 expression and halting TNFα/NFκB/NLRP3 inflammatory pathway.

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Section: Discussionmentioning

confidence: 95%

Protective effect ofMorus macrouraMiq. fruit extract against acetic acid-induced ulcerative colitis in rats: Involvement of miRNA-223 and TNFα/NFκB/NLRP3 inflammatory pathway

Salama

Darwish

Shaffei

et al. 2020

Preprint

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“…Microglia were cultured in DMEM (#41500034, GIBCO, China) medium containing 10% FBS (#10099141, GIBCO, China), placed at 37°C, and cultivated in a humidity chamber with 5% CO 2 . Lipopolysaccharide (LPS) induces inflammation of microglia [ 18 ], which is divided into two groups: Control group and LPS group (given with a final concentration of 1.0 μ g/mL LPS) [ 19 , 20 ]. The short hairpin targeting EZH2 (sh-EZH2) and sh-NC were synthesized by Sangon Biotech (Shanghai, China) for knockdown EZH2 expression.…”

Section: Methodsmentioning

confidence: 99%

EZH2 Mediates miR-146a-5p/HIF-1α to Alleviate Inflammation and Glycolysis after Acute Spinal Cord Injury

Yang

Xia

et al. 2021

Mediators of Inflammation

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Acute spinal cord injury (ASCI) is a severe traumatic disease of the central nervous system, the underlying mechanism of which is unclear. This study was intended to study the role of EZH2 and miR-146a-5p/HIF-1α in inflammation and glycolysis after ASCI, providing reference and basis for the clinical treatment and prognosis of ASCI injury. We used lipopolysaccharide (LPS) to induce inflammation of microglia, and we constructed the ASCI animal model. qRT-PCR detected the relative expression levels of EZH2, HIF-1α, miR-146a-5p, IL-6, TNF-α, IL-17, PKM2, GLUT1, and HK2 in cells and tissues. Western blot was performed to detect the expression levels of EZH2, HIF-1α, H3K27me3, IL-6, TNF-α, IL-17, PKM2, GLUT1, and HK2. ChIP verified the enrichment of H3K27me3 in the miR-146a-5p promoter region. Bioinformatics predicted the binding sites of HIF-1α and miR-146a-5p, and dual-luciferase reporter assay verified the binding of HIF-1α and miR-146a-5p. ELISA detects the levels of inflammatory factors IL-6, TNF-α, and IL-17 in the cerebrospinal fluid of rats. The GC-TOFMS was used to detect the changes of glycolytic metabolites in the cerebrospinal fluid of rats. EZH2 could mediate inflammation and glycolysis of microglia. EZH2 regulates inflammation and glycolysis through HIF-1α. EZH2 indirectly regulated the HIF-1α expression by mediating miR-146a-5p. EZH2 mediates miR-146a-5p/HIF-1α to alleviate inflammation and glycolysis in ASCI rats. In the present study, our results demonstrated that EZH2 could mediate miR-146a-5p/HIF-1α to alleviate the inflammation and glycolysis after ASCI. Therefore, EZH2/miR-146a-5p/HIF-1α might be a novel potential target for treating ASCI.

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“…Studies have shown that miR-223 levels are significantly increased after acute SCI, and inhibition of miR-223 aggravates injury and inflammatory response, while overexpression has the opposite effect. The author and colleagues also found that overexpression of miR-223 in microglia inhibits LPS-induced inflammation (Zhang et al, 2020). In addition to what has been described above, several other miRNAs have been shown to be involved in the activation of NLRP3 inflammasome and have shown efficacy in CNS trauma disease models, including miR-423-5p, miR-34c, and miR-193a (Xu et al, 2019;Si et al, 2020;Cheng et al, 2021).…”

Section: Mir-223mentioning

confidence: 89%

TI: NLRP3 Inflammasome-Dependent Pyroptosis in CNS Trauma: A Potential Therapeutic Target

Conghui

Zheng

Fan

et al. 2022

Front. Cell Dev. Biol.

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Central nervous system (CNS) trauma, including traumatic brain injury (TBI) and traumatic spinal cord injury (SCI), is characterized by high morbidity, disability, and mortality. TBI and SCI have similar pathophysiological mechanisms and are often accompanied by serious inflammatory responses. Pyroptosis, an inflammation-dependent programmed cell death, is becoming a major problem in CNS post-traumatic injury. Notably, the pyrin domain containing 3 (NLRP3) inflammasome is a key protein in the pyroptosis signaling pathway. Therefore, underlying mechanism of the NLRP3 inflammasome in the development of CNS trauma has attracted much attention. In this review, we briefly summarize the molecular mechanisms of NLRP3 inflammasome in pyroptosis signaling pathway, including its prime and activation. Moreover, the dynamic expression pattern, and roles of the NLRP3 inflammasome in CNS post-traumatic injury are summarized. The therapeutic applications of NLRP3 inflammasome activation inhibitors are also discussed.

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MicroRNA-223 targets NLRP3 to relieve inflammation and alleviate spinal cord injury

Cited by 29 publications

References 37 publications

Protective effect ofMorus macrouraMiq. fruit extract against acetic acid-induced ulcerative colitis in rats: Involvement of miRNA-223 and TNFα/NFκB/NLRP3 inflammatory pathway

Protective effect ofMorus macrouraMiq. fruit extract against acetic acid-induced ulcerative colitis in rats: Involvement of miRNA-223 and TNFα/NFκB/NLRP3 inflammatory pathway

EZH2 Mediates miR-146a-5p/HIF-1α to Alleviate Inflammation and Glycolysis after Acute Spinal Cord Injury

TI: NLRP3 Inflammasome-Dependent Pyroptosis in CNS Trauma: A Potential Therapeutic Target

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