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MicroRNA regulation of macrophages in human pathologies

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Abstract

Macrophages play a crucial role in the innate immune system and contribute to a broad spectrum of pathologies, like in the defence against infectious agents, in inflammation resolution, and wound repair. In the past several years, microRNAs (miRNAs) have been demonstrated to play important roles in immune diseases by regulating macrophage functions. In this review, we will summarize the role of miRNAs in the differentiation of monocytes into macrophages, in the classical and alternative activation of macrophages, and in the regulation of phagocytosis and apoptosis. Notably, miRNAs preferentially target genes related to the cellular cholesterol metabolism, which is of key importance for the inflammatory activation and phagocytic activity of macrophages. miRNAs functionally link various mechanisms involved in macrophage activation and contribute to initiation and resolution of inflammation. miRNAs represent promising diagnostic and therapeutic targets in different conditions, such as infectious diseases, atherosclerosis, and cancer.

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Abbreviations

M-CSF:

Macrophage colony stimulating factor

GM-CSF:

Granulocyte-macrophage colony-stimulating factor

CSF1R:

Macrophage colony stimulating factor receptor

PU.1:

Purine-rich PU-box-binding protein 1

SREBP:

Sterol regulatory element binding protein

PRRs:

Pattern-recognition receptors

TLRs:

Toll-like receptors

IFN-γ:

Interferon gamma

IL:

Interleukin

TNF:

Tumor necrosis factor

ROS:

Reactive oxygen species

NF-κB:

Nuclear factor-κB

LPS:

Lipopolysaccharide

PPARγ:

Peroxisome proliferator-activated receptor gamma

JAK:

Janus kinases

STAT1:

Signal transducers and activators of transcription 1

PI3K:

Phosphatidylinositol 3-kinase

Akt:

Thymoma viral proto-oncogene

HIF-1:

Hypoxia-inducible factor-1

OXPHOS:

Oxidative phosphorylation

miRNAs:

MicroRNAs

UTR:

Untranslated region

C/EBP-α:

CCAAT/enhancer binding protein alpha

ACVR1B:

Activin A receptor type IB

Ets E26:

Avian leukemia oncogene

Bmpr2:

Bone morphogenetic protein receptor type-2

OxLDL:

Oxidized low-density lipoprotein

SOCS1:

Suppressor of cytokine signaling 1

Bcl6:

B cell leukemia/lymphoma 6

FADD:

Fas-associated death domain-containing protein

Ccl2:

Chemokine (C–C motif) ligand 2

Erk:

Mitogen-activated protein kinase 1

APOE:

Apolipoprotein E

TRAF6:

TNF receptor-associated factor 6

IRAK1:

IL-1 receptor-associated kinase 1

IRF5:

Interferon regulatory factor 5

TMEM49:

Transmembrane protein 19

PDCD4:

Programmed cell death 4

PTEN:

Phosphatase and tensin homolog

Egr2:

Early growth response 2

LXR:

Liver X receptor

ABCA1:

ATP binding cassette subfamily A member 1

ABCG1:

ATP binding cassette subfamily G member 1

ACAT1:

Acetyl-CoA acetyltransferase 1

CE:

Cholesteryl ester

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Acknowledgments

A.S. acknowledges support from the Deutsche Forschungsgemeinschaft (SFB 1123-B4), the German Center for Cardiovascular Research, and the German Federal Ministry of Education and Research (Grant number 01KU1213A). A.S. and Y.W. acknowledge support from Else Kröner-Fresenius-Stiftung (Grant number 2014_A219).

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  1. Experimental Vascular Medicine, Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Pettenkoferstrasse 9, 80336, Munich, Germany

    Yuanyuan Wei & Andreas Schober

  2. DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, 80802, Munich, Germany

    Yuanyuan Wei & Andreas Schober

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Wei, Y., Schober, A. MicroRNA regulation of macrophages in human pathologies. Cell. Mol. Life Sci. 73, 3473–3495 (2016). https://doi.org/10.1007/s00018-016-2254-6

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