MicroRNA-150 targets PU.1 and regulates macrophage differentiation and function in experimental autoimmune encephalomyelitis

Shakerian, Leila; Ghorbani, Samira; Talebi, Fatemeh; Noorbakhsh, Farshid

doi:10.1016/j.jneuroim.2018.06.010

Cited by 25 publications

(17 citation statements)

References 62 publications

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“…In a study on Alzheimer's disease, downregulation of PU.1 in BV2 cells suppressed the expression of pro-inflammatory genes, such as CCL2 and IL-1β, as well as Aif1 (also known as Iba1), a molecular marker of microglia [37]. In another study with BMDM, miR-150-induced PU.1 downregulation inhibited the expression of pro-inflammatory cytokines and shifted the macrophage polarization toward the M2 state [42]. In a recent study of EAE mice, CNS microglia switched toward the M2 phenotype after BSYS (a traditional Chinese medicine) treatment.…”

Section: Discussionmentioning

confidence: 97%

MicroRNA-124 Alleviates Retinal Vasoregression via Regulating Microglial Polarization

Chen

Lin

Schlotterer

et al. 2021

IJMS

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Microglial activation is implicated in retinal vasoregression of the neurodegenerative ciliopathy-associated disease rat model (i.e., the polycystic kidney disease (PKD) model). microRNA can regulate microglial activation and vascular function, but the effect of microRNA-124 (miR-124) on retinal vasoregression remains unclear. Transgenic PKD and wild-type Sprague Dawley (SD) rats received miR-124 at 8 and 10 weeks of age intravitreally. Retinal glia activation was assessed by immunofluorescent staining and in situ hybridization. Vasoregression and neuroretinal function were evaluated by quantitative retinal morphometry and electroretinography (ERG), respectively. Microglial polarization was determined by immunocytochemistry and qRT-PCR. Microglial motility was examined via transwell migration assays, wound healing assays, and single-cell tracking. Our data showed that miR-124 inhibited glial activation and improved vasoregession, as evidenced by the reduced pericyte loss and decreased acellular capillary formation. In addition, miR-124 improved neuroretinal function. miR-124 shifted microglial polarization in the PKD retina from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype by suppressing TNF-α, IL-1β, CCL2, CCL3, MHC-II, and IFN-γ and upregulating Arg1 and IL-10. miR-124 also decreased microglial motility in the migration assays. The transcriptional factor of C/EBP-α-PU.1 signaling, suppressed by miR-124 both in vivo (PKD retina) and in vitro (microglial cells), could serve as a key regulator in microglial activation and polarization. Our data illustrate that miR-124 regulates microglial activation and polarization. miR-124 inhibits pericyte loss and thereby alleviates vasoregression and ameliorates neurovascular function.

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Section: Discussionmentioning

confidence: 97%

MicroRNA-124 Alleviates Retinal Vasoregression via Regulating Microglial Polarization

Chen

Lin

Schlotterer

et al. 2021

IJMS

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“…miR-150 was identified as differentially regulated during the maturation of human monocytes into macrophages, where it was downregulated in macrophages compared to monocytes [41]. miR-150 expression was also decreased in LPS-stimulated murine BMDMs, which negatively correlated with PU.1 transcript expression, suggesting that miR-150 is inflammation responsive and may also interact with PU.1 [62]. Luciferase assays confirmed that miR-150 directly targeted the PU.1 transcript.…”

Section: Expression Analysis Identified De Mirnas Known To Be Involved In Macrophage Function or Differentiation In Other Species And/or mentioning

confidence: 91%

“…Luciferase assays confirmed that miR-150 directly targeted the PU.1 transcript. Furthermore, the overexpression of miR-150 in murine BMDMs significantly reduced PU.1 transcript expression and shifted polarization away from M1 [62].…”

Section: Expression Analysis Identified De Mirnas Known To Be Involved In Macrophage Function or Differentiation In Other Species And/or mentioning

confidence: 96%

Characterization of miRNAs in Cultured Atlantic Salmon Head Kidney Monocyte-Like and Macrophage-Like Cells

Smith

Christian

Woldemariam

et al. 2020

IJMS

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Macrophages are among the first cells to respond to infection and disease. While microRNAs (miRNAs) are involved in the process of monocyte-to-macrophage differentiation in mammals, less is known in teleost fish. Here, Atlantic salmon head kidney leukocytes (HKLs) were used to study the expression of miRNAs in response to in vitro culture. The morphological analysis of cultures showed predominantly monocyte-like cells on Day 1 and macrophage-like cells on Day 5, suggesting that the HKLs had differentiated from monocytes to macrophages. Day 5 HKLs also contained a higher percentage of phagocytic cells. Small RNA sequencing and qPCR analysis were applied to examine the miRNA diversity and expression. There were 370 known mature Atlantic salmon miRNAs in HKLs. Twenty-two miRNAs (15 families) were downregulated while 44 miRNAs (25 families) were upregulated on Day 5 vs. Day 1. Mammalian orthologs of many of the differentially expressed (DE) miRNAs are known to regulate macrophage activation and differentiation, while the teleost-specific miR-2188, miR-462 and miR-731 were also DE and are associated with immune responses in fish. In silico predictions identified several putative target genes of qPCR-validated miRNAs associated with vertebrate macrophage differentiation. This study identified Atlantic salmon miRNAs likely to influence macrophage differentiation, providing important knowledge for future functional studies.

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“…Numerous studies including ours have reported a strong correlation between altered miRNA expression levels and secondary brain injury events (Liu et al 2014;Redell et al 2009; Wang et al 2015). Among these altered miRNAs, miR-146a, miR-223-3p, miR-155-5p, and miR-150 play key roles in in ammatory signaling (Cardoso et al 2012;Zhao et al 2011;Johnnidis et al 2008;Shakerian et al 2018). However, a mechanistic role for these in ammatory miRNAs in TBI-induced neuroin ammation is poorly understood.…”

Section: Introductionmentioning

confidence: 74%

Sex-Specific Alterations in Inflammatory MicroRNAs in Mouse Brain and Bone Marrow CD11b+ Cells Following Traumatic Brain Injury

Prajapati

Wang

Pesina

et al. 2021

Preprint

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Sex is a key biological variable in traumatic brain injury (TBI) and plays a significant role in neuroinflammatory responses. However, the molecular mechanisms contributing to this sexually dimorphic neuroinflammatory response remain elusive. Here we describe a significant and previously unreported tissue enrichment and sex specific alteration of a set of inflammatory microRNAs (miRNAs) in CD11b + cells of brain and bone marrow isolated from naïve mice as well as mice subjected to TBI. Our data from naïve mice demonstrated that expression levels of miR-146a-5p and miR-150-5p were relatively higher in brain CD11b + cells, and that miR-155-5p and miR-223-3p were highly enriched in bone marrow CD11b + cells. Furthermore, while miR-150-5p and miR-155-5p levels were higher in male brain CD11b + cells, no significant sexual difference was observed for miR-146a-5p and miR-223-3p. However, TBI resulted in sex specific differential responses of these miRNAs in brain CD11b + cells. Specifically, miR-223 levels in brain CD11b + cells were markedly elevated in both sexes in response to TBI at 3 and 24 hr, with levels in females being significantly higher than males at 24 hr. We then focused on analyzing several miR-223-3p targets and inflammation-related marker genes following injury. Corresponding to the greater elevation of miR-223-3p in females, the miR-223-3p targets, TRAF6 and FBXW7 were significantly reduced in females compared to males. Interestingly, anti-inflammatory genes ARG1 and IL4 were higher in females after TBI than in males. These observations suggest miR-223-3p and other inflammatory responsive miRNAs may play a key role in sex-specific neuroinflammatory response following TBI.

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MicroRNA-150 targets PU.1 and regulates macrophage differentiation and function in experimental autoimmune encephalomyelitis

Cited by 25 publications

References 62 publications

MicroRNA-124 Alleviates Retinal Vasoregression via Regulating Microglial Polarization

MicroRNA-124 Alleviates Retinal Vasoregression via Regulating Microglial Polarization

Characterization of miRNAs in Cultured Atlantic Salmon Head Kidney Monocyte-Like and Macrophage-Like Cells

Sex-Specific Alterations in Inflammatory MicroRNAs in Mouse Brain and Bone Marrow CD11b+ Cells Following Traumatic Brain Injury

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