CD14 gene silencing alters the microRNA expression profile of RAW264.7 cells stimulated by <i>Brucella melitensis</i> infection

Hui, Rutai; Hu, Jiao; Hao, Yuanyuan; Pang, Feng; Li, Guohua; Peng, Dongmei; Li, Yaying; Wang, Yuanzhi; Zhang, Hui; Fan, Qing; Chen, Chuangfu; Du, Lijun

doi:10.1177/1753425917707025

Cited by 10 publications

(12 citation statements)

References 22 publications

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“…However, both the p-Akt/p-Erk pathways were soon downregulated, which was associated with rapid degradation of TrkA in response to NGF stimulation and the overexpression of Cblb and Cbl genes. Similar to Takahashi's results [27][28][29][30], our co-IP data showed that TrkA ubiquitination and degradation were statistically affected by Cbl, but the domain of TrkA required for ubiquitination by Cbl remains unclear. The mechanisms of the TrkA-Cblb interaction may involve the TKB domain (an SH2like domain) promoting the binding of phosphorylated tyrosine on activated TrkA and Src homology 2 adapter Fig.…”

Section: Discussionsupporting

confidence: 89%

“…Through an in vitro study, we determined that the Cbl mRNA 3′ UTR was the target of miR-145-5p and that the Cblb mRNA 3′UTR was the target of miR-199a-3p. The predicted biding site of Cbl mRNA for miR-145-5p is first reported and proved by us; interestingly, the predicted biding site of Cblb mRNA for miR-199a-3p was previously reported but not examined in RAW264.7 cells by Rong [29].…”

Section: Discussionmentioning

confidence: 68%

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Umbilical mesenchymal stem cell-derived exosomes facilitate spinal cord functional recovery through the miR-199a-3p/145-5p-mediated NGF/TrkA signaling pathway in rats

Wang

Lai

et al. 2021

Stem Cell Res Ther

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Background Although exosomes, as byproducts of human umbilical cord mesenchymal stem cells (hUC-MSCs), have been demonstrated to be an effective therapy for traumatic spinal cord injury (SCI), their mechanism of action remains unclear. Methods We designed and performed this study to determine whether exosomes attenuate the lesion size of SCI by ameliorating neuronal injury induced by a secondary inflammatory storm and promoting neurite outgrowth. We determined the absolute levels of all exosomal miRNAs and investigated the potential mechanisms of action of miR-199a-3p/145-5p in inducing neurite outgrowth in vivo and in vitro. Results miR-199a-3p/145-5p, which are relatively highly expressed miRNAs in exosomes, promoted PC12 cell differentiation suppressed by lipopolysaccharide (LPS) in vitro through modulation of the NGF/TrkA pathway. We also demonstrated that Cblb was a direct target of miR-199a-3p and that Cbl was a direct target of miR-145-5p. Cblb and Cbl gene knockdown resulted in significantly decreased TrkA ubiquitination levels, subsequently activating the NGF/TrkA downstream pathways Akt and Erk. Conversely, overexpression of Cblb and Cbl was associated with significantly increased TrkA ubiquitination level, subsequently inactivating the NGF/TrkA downstream pathways Akt and Erk. Western blot and coimmunoprecipitation assays confirmed the direct interaction between TrkA and Cblb and TrkA and Cbl. In an in vivo experiment, exosomal miR-199a-3p/145-5p was found to upregulate TrkA expression at the lesion site and also promote locomotor function in SCI rats. Conclusions In summary, our study showed that exosomes transferring miR-199a-3p/145-5p into neurons in SCI rats affected TrkA ubiquitination and promoted the NGF/TrkA signaling pathway, indicating that hUC-MSC-derived exosomes may be a promising treatment strategy for SCI.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 68%

Umbilical mesenchymal stem cell-derived exosomes facilitate spinal cord functional recovery through the miR-199a-3p/145-5p-mediated NGF/TrkA signaling pathway in rats

Wang

Lai

et al. 2021

Stem Cell Res Ther

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“…The authors observed up-regulation of mmu-miR-199a-3p and mmu-miR-183-5p. Interestingly, among the predicted target genes of mmu-miR-199a-3p and mmu-miR-183-5p, the significantly enriched gene ontology terms were the apoptosis process, immune response, inflammatory response, innate immune response, anti-apoptosis, cytokine production, and cytokine-mediated signalling pathway [ 37 ]. In one of our previous studies, more than 2,000 miRNAs were screened in peripheral blood mononuclear cells of patients with acute or chronic brucellosis, and we determined that while the expression level of miR-1238-3p increased, miR-494, miR-6069, and miR-139-3p decreased in the chronic group compared to the acute group.…”

Section: Discussionmentioning

confidence: 99%

The microRNA expression signature of CD4+ T cells in the transition of brucellosis into chronicity

et al. 2018

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Brucellosis is a serious infectious disease that continues to be a significant cause of morbidity worldwide and across all ages. Despite early diagnosis and treatment, 10–30% of patients develop chronic brucellosis. Although there have been recent advances in our knowledge of Brucella virulence factors and hosts’ immune response to the infection, there is a lack of clear data regarding how the infection bypasses the immune system and becomes chronic. The present study investigated immunological factors and their roles in the transition of brucellosis from an acute to a chronic infection in CD4+ T cells. CD4+ T cells sorted from peripheral blood samples of patients with acute or chronic brucellosis and healthy controls using flow cytometry as well as more than 2000 miRNAs were screened using the GeneSpring GX (Agilent) 13.0 miRNA microarray software and were validated using reverse transcription polymerase chain reaction (RT-qPCR). Compared to acute cases, the expression levels of 28 miRNAs were significantly altered in chronic cases. Apart from one miRNA (miR-4649-3p), 27 miRNAs were not expressed in the acute cases (p <0.05, fold change> 2). According to KEGG pathway analysis, these miRNAs are involved in the regulation of target genes that were previously involved in the MAPK signalling pathway, regulation of the actin cytoskeleton, endocytosis, and protein processing in the endoplasmic reticulum. This indicates the potential role of these miRNAs in the development of chronic brucellosis. We suggest that these miRNAs can be used as markers to determine the transition of the disease into chronicity. This is the first study of miRNA expression that analyses human CD4+ T cells to clarify the mechanism of chronicity in brucellosis.

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“…Recently, the ability of another chronic intracellular pathogen, Mycobacterium tuberculosis, to manipulate host innate responses, autophagy, and apoptosis via host miRNA has garnered much interest [43][44][45][46]. In contrast, there is much less information regarding miRNA in the context of Brucella infection [47][48][49]. Budak et al investigated the miRNA expression patterns in CD4+ and CD8+ T cells from patients, and reported discrete changes with acute vs. chronic brucellosis [50,51].…”

Section: Discussionmentioning

confidence: 99%

Brucella suppress STING expression via miR-24 to enhance infection

et al. 2020

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Brucellosis, caused by a number of Brucella species, remains the most prevalent zoonotic disease worldwide. Brucella establish chronic infections within host macrophages despite triggering cytosolic innate immune sensors, including Stimulator of Interferon Genes (STING), which potentially limit infection. In this study, STING was required for control of chronic Brucella infection in vivo. However, early during infection, Brucella down-regulated STING mRNA and protein. Down-regulation occurred post-transcriptionally, required live bacteria, the Brucella type IV secretion system, and was independent of host IRE1-RNase activity. STING suppression occurred in MyD88-/- macrophages and was not induced by Toll-like receptor agonists or purified Brucella lipopolysaccharide (LPS). Rather, Brucella induced a STING-targeting microRNA, miR-24-2, in a type IV secretion system-dependent manner. Furthermore, STING downregulation was inhibited by miR-24 anti-miRs and in Mirn23a locus-deficient macrophages. Failure to suppress STING expression in Mirn23a-/- macrophages correlated with diminished Brucella replication, and was rescued by exogenous miR-24. Mirn23a-/- mice were also more resistant to splenic colonization one week post infection. Anti-miR-24 potently suppressed replication in wild type, but much less in STING-/- macrophages, suggesting most of the impact of miR-24 induction on replication occurred via STING suppression. In summary, Brucella sabotages cytosolic surveillance by miR-24-dependent suppression of STING expression; post-STING activation “damage control” via targeted STING destruction may enable establishment of chronic infection.

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CD14 gene silencing alters the microRNA expression profile of RAW264.7 cells stimulated by Brucella melitensis infection

Cited by 10 publications

References 22 publications

Umbilical mesenchymal stem cell-derived exosomes facilitate spinal cord functional recovery through the miR-199a-3p/145-5p-mediated NGF/TrkA signaling pathway in rats

Umbilical mesenchymal stem cell-derived exosomes facilitate spinal cord functional recovery through the miR-199a-3p/145-5p-mediated NGF/TrkA signaling pathway in rats

The microRNA expression signature of CD4+ T cells in the transition of brucellosis into chronicity

Brucella suppress STING expression via miR-24 to enhance infection

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