MicroRNA‐93 inhibits inflammatory cytokine production in LPS‐stimulated murine macrophages by targeting IRAK4

Xu, Yan; Jin, Huiyi; Yang, Xiaolu; Wang, Lili; Su, Li; Liu, Kun; Gu, Qing; Xu, Xun

doi:10.1016/j.febslet.2014.03.013

Cited by 45 publications

(30 citation statements)

References 25 publications

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“…2014; Xu et al. 2014). miR‐17‐5p, which was detected to be downregulated in our study group, has also been considered to be a regulatory intermediate of multiple MAPKs (Cloonan et al.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA regulation in an animal model of acute ocular hypertension

Wang

Valiente‐Soriano

Nadal-Nicolás

et al. 2016

Acta Ophthalmologica

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PurposeTo analyse miRNA regulation in a rat model of acute ocular hypertension (AOH).MethodsAcute ocular hypertension (AOH) was induced in the left eye of adult albino rats by inserting a cannula connected with a saline container into the anterior chamber. The contralateral eye served as a control. Seven days later, animals were killed. Retinas were used either for quantitative analysis of retinal ganglion cells (RGCs) and microglial cells or for miRNA array hybridization, qRT‐PCR and Western blotting.ResultsAnatomically, AOH caused axonal degeneration, a significant loss of RGCs and a significant increase in microglial cells in the ganglion cell layer. The miRNAs microarray analysis revealed 31 differentially expressed miRNAs in the AOH versus control group, and the regulation of 12 selected microRNAs was further confirmed by qRT‐PCR. Bioinformatic analysis indicates that several signalling pathways are putatively regulated by the validated miRNAs. Of particular interest was the inflammatory pathway signalled by mitogen‐activated protein kinases (MAPKs). In agreement with the in silico analysis, p38 MAP kinase, tumour necrosis factor‐alpha (TNF‐α) and iNOS proteins were significantly upregulated in the AOH retinas.ConclusionsAcute IOP elevation led to changes in the expression of miRNAs, whose target genes were associated with the regulation of microglia‐mediated neuroinflammation or neural apoptosis. Addressing miRNAs in the process of retinal ischaemia and optic nerve damage in association with high IOP elevation may open new avenues in preventing retinal ganglion cell apoptosis and may serve as target for future therapeutic regimen in acute ocular hypertension and retinal ischaemic conditions.

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“…2014; Xu et al. 2014). miR‐17‐5p, which was detected to be downregulated in our study group, has also been considered to be a regulatory intermediate of multiple MAPKs (Cloonan et al.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA regulation in an animal model of acute ocular hypertension

Wang

Valiente‐Soriano

Nadal-Nicolás

et al. 2016

Acta Ophthalmologica

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“…On the other hand, some miRNAs have been shown to be downregulated by LPS. miR-93 expression in LPS-stimulated macrophages was significantly decreased and contributed to the inflammatory cytokine production in LPSstimulated murine macrophages (Xu et al, 2014); miR-98 was also downregulated in macrophages after LPS stimulation, and accounted for the IL-10 production and endotoxin tolerance (Liu et al, 2011). The LPS-downregulated miR-210 also negatively regulated the LPS-induced production of proinflammatory cytokines by targeting NF-κB1 (Qi et al, 2012).…”

Section: Mir-23b Ameliorates Lps Inhibition Of Bmp-2-induced Osteogenmentioning

confidence: 98%

miR-23b targets Smad 3 and ameliorates the LPS-inhibited osteogenic differentiation in preosteoblast MC3T3-E1 cells

Liu

Wang

et al. 2016

J. Toxicol. Sci.

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-Lipopolysaccharide (LPS) has been confirmed to be the main inhibitor in osteogenic differentiation, posing a clinical challenge to bone healing, particularly for trauma followed by endotoxinemia/sepsis. However, the molecular mechanism remains ambiguous. miR-23b, which regulates multiple signaling pathways in inflammation, has been shown to be deregulated by LPS. In this study, we examined the LPS-mediated regulation on the expression of miR-23b and Smad 3 in preosteoblast MC3T3-E1 cells. Then we determined the regulation of miR-23b overexpression on the Smad 3 expression and on the LPS-mediated inhibition of bone morphogenetic protein-2 (BMP-2)-induced osteogenic differentiation. Our results demonstrated that LPS significantly downregulated the expression of miR-23b, while upregulating Smad 3 in MC3T3-E1 cells. However, the transfection with miR-23b mimics markedly downregulated the Smad 3 in both mRNA and protein levels, via the specific binding to the 3'-untranslated region (UTR) of Smad 3. Moreover, though LPS markedly downregulated the BMP-2-induced osteogenic differentiation of MC3T3-E1 cells by inhibiting the expression of alkaline phosphatase (ALP), Osteocalcin (OCN), Osteopontin (OPN) and Runt-related transcription factor 2 (RUNX2). The upregulated miR-23b reversed such downregulation of ALP, OCN, OPN and RUNX2 in the MC3T3-E1 cells which were treated both with LPS and BMP-2. In conclusion, our data indicates that miR-23b ameliorates the LPS-mediated inhibition of BMP-2-induced osteogenic differentiation in MC3T3-E1 cells, implying the protective role of miR-23b in the LPS-mediated inhibition of osteogenic differentiation and bone formation.

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“…Targets of these miRNA families are enriched for antiviral and cytotoxic transcripts and miR-93 was recently shown to silence inflammatory cytokines [22, 74]. PARP13-mediated repression of the miRNA pathway, therefore, facilitates the expression of antiviral transcripts, and promotes the switch to an antiviral state [22].…”

Section: Parp13 and Disease: Innate Immunitymentioning

confidence: 99%

Poly(ADP-ribose) polymerase-13 and RNA regulation in immunity and cancer

Todorova

Bock

Chang

2015

Trends in Molecular Medicine

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Posttranscriptional regulation of RNA is an important mechanism for activating and resolving cellular stress responses. Poly(ADP-ribose) Polymerase-13 (PARP13), also known as ZC3HAV1 and Zinc-finger Antiviral Protein (ZAP), is an RNA-binding protein that regulates the stability, and translation of specific mRNAs, and modulates the miRNA silencing pathway to globally impact miRNA targets. These functions of PARP13 are important components of the cellular response to stress. In addition, the ability of PARP13 to restrict oncogenic viruses and to repress the pro-survival cytokine receptor TRAILR4 suggests that it can be protective against malignant transformation and cancer development. The relevance of PARP13 to human health and disease make it a promising therapeutic target.

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MicroRNA‐93 inhibits inflammatory cytokine production in LPS‐stimulated murine macrophages by targeting IRAK4

Cited by 45 publications

References 25 publications

MicroRNA regulation in an animal model of acute ocular hypertension

MicroRNA regulation in an animal model of acute ocular hypertension

miR-23b targets Smad 3 and ameliorates the LPS-inhibited osteogenic differentiation in preosteoblast MC3T3-E1 cells

Poly(ADP-ribose) polymerase-13 and RNA regulation in immunity and cancer

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