MicroRNA Milk Exosomes: From Cellular Regulator to Genomic Marker

Michela Cintio; Giulia Polacchini; Elisa Scarsella; Tommaso Montanari; Bruno Stefanon; Monica Colitti

doi:10.3390/ani10071126

MicroRNA Milk Exosomes: From Cellular Regulator to Genomic Marker

Animals ◽

10.3390/ani10071126 ◽

2020 ◽

Vol 10 (7) ◽

pp. 1126 ◽

Cited By ~ 2

Author(s):

Michela Cintio ◽

Giulia Polacchini ◽

Elisa Scarsella ◽

Tommaso Montanari ◽

Bruno Stefanon ◽

...

Keyword(s):

Dna Methyltransferase ◽

Target Genes ◽

Cell Communication ◽

Cell Functions ◽

Genomic Marker ◽

Genomic Markers ◽

Cellular Signaling Pathway ◽

Selective Delivery ◽

Specific Regulation

Recent advances in ruminants’ milk-derived exosomes (EXO) have indicated a role of microRNAs (miRNAs) in cell-to-cell communication in dairy ruminants. The miRNAs EXO retain peculiar mechanisms of uptake from recipient cells, which enables the selective delivery of cargos, with a specific regulation of target genes. Although many studies have been published on the miRNAs contained in milk, less information is available on the role of miRNAs EXO, which are considered stable over time and resistant to digestion and milk processing. Several miRNAs EXO have been implicated in the cellular signaling pathway, as in the regulation of immune response. Moreover, they exert epigenetic control, as extenuating the expression of DNA methyltransferase 1. However, the study of miRNAs EXO is still challenging due to the difficulty of isolating EXO. In fact, there are not agreed protocols, and different methods, often time-consuming, are used, making it difficult to routinely process a large number of samples. The regulation of cell functions in mammary glands by miRNAs EXO, and their applications as genomic markers in livestock, is presented.

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Nutrients and Immunometabolism: Role of Macrophage NLRP3

Journal of Nutrition ◽

10.1093/jn/nxaa085 ◽

2020 ◽

Vol 150 (7) ◽

pp. 1693-1704

Author(s):

Kate J Claycombe-Larson ◽

Travis Alvine ◽

Dayong Wu ◽

Nishan S Kalupahana ◽

Naima Moustaid-Moussa ◽

...

Keyword(s):

Nlrp3 Inflammasome ◽

Tissue Cell ◽

Cell Functions ◽

Pyrin Domain ◽

Increased Risk ◽

Vital Cell ◽

Cell Type Specific ◽

Specific Regulation

ABSTRACT Inflammation is largely mediated by immune cells responding to invading pathogens, whereas metabolism is oriented toward producing usable energy for vital cell functions. Immunometabolic alterations are considered key determinants of chronic inflammation, which leads to the development of chronic diseases. Studies have demonstrated that macrophages and the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome are activated in key metabolic tissues to contribute to increased risk for type 2 diabetes mellitus, Alzheimer disease, and liver diseases. Thus, understanding the tissue-/cell-type–specific regulation of the NLRP3 inflammasome is crucial for developing intervention strategies. Currently, most of the nutrients and bioactive compounds tested to determine their inflammation-reducing effects are limited to animal models. Future studies need to address how dietary compounds regulate immune and metabolic cell reprograming in humans.

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MicroRNA miR-7 and miR-17-92 in POMC neurons are associated with sex-specific regulation of diet-induced obesity

10.1101/366419 ◽

2018 ◽

Author(s):

Yanxia Gao ◽

Jiaheng Li ◽

Zhen Zhang ◽

Ruihan Zhang ◽

Andrew Pollock ◽

...

Keyword(s):

Target Genes ◽

Profile Analysis ◽

Adult Mice ◽

Diet Induced Obesity ◽

Expression Profile Analysis ◽

Specific Regulation ◽

Underlying Mechanisms ◽

Specific Diet ◽

Differential Genes

AbstractProopiomelanocortin (POMC) neurons in the arcuate nucleus (ARC) in mammalian hypothalamus play important roles in regulating appetite, energy expenditure, and glucose and fat metabolisms. Diet-induced obesity often show sex-specific difference. But the underlying mechanisms remain unclear. Here we show that microRNA (miRNA) miR-7 and miR-17-92 are expressed in the mouse ARC, and mostly in POMC neurons. Knockdown of miR-7 and knockout of miR-17-92 specifically in POMC neurons aggravate diet-induced obesity only in females and males, respectively. Moreover, gene expression profile analysis identifies sex-differential genes in male and female ARCs in wildtype adult mice. Interestingly, these genes that normally show low-expression in the female and male ARCs display upregulated expression in female miR-7 knockdown and male miR-17-92 knockout mice, respectively. Our results demonstrate an important role of miRNAs in regulating sex-specific diet-induced obesity, likely through modulating expression of target genes that show sex-differential expression in the ARC of hypothalamus.

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The Role of PPARs in Disease

Cells ◽

10.3390/cells9112367 ◽

2020 ◽

Vol 9 (11) ◽

pp. 2367

Author(s):

Nicole Wagner ◽

Kay-Dietrich Wagner

Keyword(s):

Target Genes ◽

Peroxisome Proliferator ◽

Downstream Target ◽

Novel Approach ◽

Pparγ Agonists ◽

Cell Type Specific ◽

Peroxisome Proliferator Activated Receptors ◽

Specific Regulation ◽

X Receptors

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that function as ligand-activated transcription factors. They exist in three isoforms: PPARα, PPARβ/δ, and PPARγ. For all PPARs, lipids are endogenous ligands, linking them directly to metabolism. PPARs form heterodimers with retinoic X receptors, and upon ligand binding, they modulate the gene expression of downstream target genes, depending on the presence of co-repressors or co-activators. This results in a complex, cell type-specific regulation of proliferation, differentiation, and cell survival. PPARs are linked to metabolic disorders and are interesting pharmaceutical targets. PPARα and PPARγ agonists are already in clinical use for the treatment of hyperlipidemia and type 2 diabetes, respectively. More recently, PPARβ/δ activation came into focus as an interesting novel approach for the treatment of metabolic syndrome and associated cardiovascular diseases; however, this has been limited due to the highly controversial function of PPARβ/δ in cancer. This Special Issue of Cells brings together the most recent advances in understanding the various aspects of the action of PPARs, and it provides new insights into our understanding of PPARs, implying also the latest therapeutic perspectives for the utility of PPAR modulation in different disease settings.

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The putative wnt receptor Xenopus frizzled-7 functions upstream of beta-catenin in vertebrate dorsoventral mesoderm patterning

Development ◽

10.1242/dev.127.9.1981 ◽

2000 ◽

Vol 127 (9) ◽

pp. 1981-1990 ◽

Cited By ~ 4

Author(s):

S. Sumanas ◽

P. Strege ◽

J. Heasman ◽

S.C. Ekker

Keyword(s):

Antisense Oligonucleotide ◽

Intracellular Signaling ◽

Target Genes ◽

Cell Communication ◽

Beta Catenin ◽

Signaling Complex ◽

Wnt Proteins ◽

Mesoderm Specification ◽

Mesoderm Patterning

We have isolated one member of the frizzled family of wnt receptors from Xenopus (Xfz7) to study the role of cell-cell communication in the establishment of the vertebrate axis. We demonstrate that this maternally encoded protein specifically synergizes with wnt proteins in ectopic axis induction. Embryos derived from oocytes depleted of maternal Xfz7 RNA by antisense oligonucleotide injection are deficient in dorsoanterior structures. Xfz7-depleted embryos are deficient in dorsal but not ventral mesoderm due to the reduced expression of the wnt target genes siamois, Xnr3 and goosecoid. These signaling defects can be restored by the addition of beta-catenin but not Xwnt8b. Xfz7 thus functions upstream of the known GSK-3/axin/beta-catenin intracellular signaling complex in vertebrate dorsoventral mesoderm specification.

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Pathophysiology of Preeclampsia: The Role of Exosomes

International Journal of Molecular Sciences ◽

10.3390/ijms22052572 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2572

Author(s):

Keiichi Matsubara ◽

Yuko Matsubara ◽

Yuka Uchikura ◽

Takashi Sugiyama

Keyword(s):

Cell Communication ◽

Extravillous Trophoblast ◽

Invasive Ability ◽

Serum Factors ◽

Cell Functions ◽

Soluble Endoglin ◽

Membrane Bound ◽

Recent Attention ◽

Fertilized Egg

The pathogenesis of preeclampsia begins when a fertilized egg infiltrates the decidua, resulting in implantation failure (e.g., due to extravillous trophoblast infiltration disturbance and abnormal spiral artery remodeling). Thereafter, large amounts of serum factors (e.g., soluble fms-like tyrosine kinase 1 and soluble endoglin) are released into the blood from the hypoplastic placenta, and preeclampsia characterized by multiorgan disorder caused by vascular disorders develops. Successful implantation and placentation require immune tolerance to the fertilized egg as a semi-allograft and the stimulation of extravillous trophoblast infiltration. Recently, exosomes with diameters of 50–100 nm have been recognized to be involved in cell–cell communication. Exosomes affect cell functions in autocrine and paracrine manners via their encapsulating microRNA/DNA and membrane-bound proteins. The microRNA profiles of blood exosomes have been demonstrated to be useful for the evaluation of preeclampsia pathophysiology and prediction of the disease. In addition, exosomes derived from mesenchymal stem cells have been found to have cancer-suppressing effects. These exosomes may repair the pathophysiology of preeclampsia through the suppression of extravillous trophoblast apoptosis and promotion of these cells’ invasive ability. Exosomes secreted by various cells have received much recent attention and may be involved in the maintenance of pregnancy and pathogenesis of preeclampsia.

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The photoreceptor cytoskeleton visualized

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100122800 ◽

1992 ◽

Vol 50 (1) ◽

pp. 480-481

Author(s):

Beth Burnside

Keyword(s):

Outer Segment ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Cell Polarization ◽

Synaptic Proteins ◽

Cell Functions ◽

Vertebrate Photoreceptor ◽

Numerous Cell ◽

Turn Over

The vertebrate photoreceptor provides a drammatic example of cell polarization. Specialized to carry out phototransduction at its distal end and to synapse with retinal interneurons at its proximal end, this long slender cell has a uniquely polarized morphology which is reflected in a similarly polarized cytoskeleton. Membranes bearing photopigment are localized in the outer segment, a modified sensory cilium. Sodium pumps which maintain the dark current critical to photosensory transduction are anchored along the inner segment plasma membrane between the outer segment and the nucleus.Proximal to the nucleus is a slender axon terminating in specialized invaginating synapses with other neurons of the retina. Though photoreceptor diameter is only 3-8u, its length from the tip of the outer segment to the synapse may be as great as 200μ. This peculiar linear cell morphology poses special logistical problems and has evoked interesting solutions for numerous cell functions. For example, the outer segment membranes turn over by means of a unique mechanism in which new disks are continuously added at the proximal base of the outer segment, while effete disks are discarded at the tip and phagocytosed by the retinal pigment epithelium. Outer segment proteins are synthesized in the Golgi near the nucleus and must be transported north through the inner segment to their sites of assembly into the outer segment, while synaptic proteins must be transported south through the axon to the synapse.The role of the cytoskeleton in photoreceptor motile processes is being intensely investigated in several laboratories.

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