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2016 ; 25
(15
): 795-804
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miRNA in Macrophage Development and Function
#MMPMID27353423
Roy S
Antioxid Redox Signal
2016[Nov]; 25
(15
): 795-804
PMID27353423
show ga
SIGNIFICANCE: MicroRNAs (miRNAs) control cellular gene expression via primarily
binding to 3' or 5' untranslated region of the target transcript leading to
translational repression or mRNA degradation. In most cases, miRNAs have been
observed to fine-tune the cellular responses and, therefore, act as a rheostat
rather than an on/off switch. Transcription factor PU.1 is a master switch that
controls monocyte/macrophage development from hematopoietic stem cells. Recent
Advances: PU.1 induces a specific set of miRNAs while suppressing the miR17-92
cluster to regulate monocyte/macrophage development. In addition to development,
miRNAs tightly control the macrophage polarization continuum from proinflammatory
M1 or proreparative M2 by regulating expression of key transcription factors
involved in the process of polarization. CRITICAL ISSUES: miRNAs are intricately
involved with fine-tuning fundamental macrophage functions such as phagocytosis,
efferocytosis, inflammation, tissue repair, and tumor promotion. Macrophages are
secretory cells that participate in intercellular communication by releasing
regulatory molecules and microvesicles (MVs). MVs are bilayered lipid membranes
packaging a hydrophilic cargo, including proteins and nucleic acids.
Macrophage-derived MVs carry functionally active miRNAs that suppress gene
expression in target cells via post-transcriptional gene silencing, thus
regulating cell function. In summary, miRNAs fine-tune several major facets of
macrophage development and function. Such fine-tuning is critical in preventing
exaggerated macrophage response to endogenous or exogenous stimuli. FUTURE
DIRECTIONS: A critical role of miRNAs in the regulation of innate immune response
and macrophage biology, including development, differentiation, and activation,
has emerged. A clear understanding of such regulation on macrophage function
remains to be elucidated. Antioxid. Redox Signal. 25, 795-804.
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