Le nouveau paradigme de l’origine développementale de la santé et des maladies (DOHaD)

Junien, Claudine; Panchenko, Polina; Pirola, Luciano; Amarger, Valérie; Kaeffer, Bertrand; Parnet, Patricia; Torrisani, Jérôme; Jimenez, Francisco Bolaños; Jammes, Hélène; Gabory, Anne

doi:10.1051/medsci/20163201006

Cited by 22 publications

(9 citation statements)

References 62 publications

(68 reference statements)

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“…Non-coding RiboNucleic Acid (small or large nc-RNA) are involved in epigenetic regulation directly silencing chromatin at specific loci by base pairing to nascent transcripts (Cech and Steitz, 2014). Among these ncRNAs, miRNAs are proposed to play a significant role in epigenetic regulation opening new avenues for therapeutic purposes (Sethupathy, 2016) or for assaying exogenous non-coding RNA acquisition on the physiology of host and putative consequences across generations (Sela et al, 2014; Junien et al, 2016). Milk contains a high amount of miRNA which has been proposed for transfer between mother and child for immune regulation (Kosaka et al, 2010), for priming the immune system of the lactating infant when from plant origin (Lukasik et al, 2017) or for trans-species effect on adult consumers through dairy products (Baier et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Oral Delivery of miRNA With Lipidic Aminoglycoside Derivatives in the Breastfed Rat

Beuzelin¹,

Pitard

Kaeffer³

2019

Front. Physiol.

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Context Specific targeting of endogenous miRNAs which are involved in epigenetics, may help understanding homeostasis with therapeutic benefits. We use new biologically inspired vehicles consisting of lipoaminoglycosides to deliver in vivo mir-320-3p, a known human breast milk exosomal miRNA, or its antagomiR. Materials and Methods Four lipoaminoglycosides were screened for cytotoxicity and their biophysical properties. 1-h breast-restricted rats received single-oral treatment of either the lipoaminoglycoside Dioleyl-Succinyl Paromomycin (DOSP) complexed with miRNA or antagomiR, or of control medium at the light on (ZeitGeber Time: ZT-0H) or off (ZT-12H). Glycemia, triglycerides, cholesterol, free-fatty acid were assayed at 0, 4, 8, and 12 h post-treatment. In the stomach, small intestine, liver, plasma, adipose tissue, plexus choroid, and cortex, relevant miRNA with precursors and mRNA (polr3d, hspb6, c-myc, stat1, clock, bmal1, per1, npas2, sirt1-6, and cyclinD1) were quantified by q-PCR. Expression of POLR3D and HSPB6 proteins were analyzed in stomach and liver by Western blot. Immunoprecipitations with anti-AGO1 and 2 were performed on nuclear and cytoplasmic fractions of gastric cells along with detection of miRNA-320-3p in nucleoli. Chromatin ImmunoPrecipitation with anti-Trimethyl-histone-3-Lys-4 and Lys-27 detecting the polr3d promoter and miR-320-3p, were performed for all groups. Results Selected DOSP (diameter: 80–200 nm) did not alter gastric extracellular vesicle secretion a few hours after intake. The miR-320-3p was mainly found in gastric or small intestinal cells, reaching the blood and liver in low amount. We have found significant up-regulation of polr3d mRNA (ANOVA, p < 0.0001) at ZT-20H for the miR-320-3p-supplemented group and a higher expression of POLR3D for antagomiR group (ANOVA, p < 0.05). We had a low accumulation of miR-320-3p at ZT-20H in nucleoli, without stat1 evolution. Delivering a high amount of miRNA or antagomiR disrupts RNA-Induced Silencing Complexes in cytoplasm triggering some transfer of extracellular molecules into nuclei with alteration of immune complexes on the polr3d promoter (with a higher amount found in the K4 histone-3-me3 immune complexes at ZT-20H). Conclusion Extracellular miRNAs embedded in DOSP have a rapid impact on RNAi and on nuclear chromatin complexes depending on the daily rhythm. An integrative view of the impact of extracellular miRNA on physiology will improve assaying epigenetic manipulations following nutritional stress.

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Section: Introductionmentioning

confidence: 99%

Oral Delivery of miRNA With Lipidic Aminoglycoside Derivatives in the Breastfed Rat

Beuzelin¹,

Pitard

Kaeffer³

2019

Front. Physiol.

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“…Таким образом, будет очень интересно оценить участие микро-РНК в координации этих различных типов клеток, необходимых для полового созревания и поддержания фертильности. Внутренняя и внешняя среда организма влияет на механизмы эпигенетического контроля, особенно те, в которых задействованы микро-РНК [30][31][32][33][34][35][36][37][38]. Поэтому создание молекулярных основ для модуляции экспрессии miRNA в соответствии с этими внутренними и внешними параметрами (биологические часы, половые гормоны, метаболический контекст, циркадный цикл, воздействие стресса, запахи и т.…”

Section: заключениеunclassified

Micro RNAS as New Players in Control of Hypothalamic Functions

Beylerli

Gareev

Beilerli

2019

Kreativnaâ hirurgiâ i onkologiâ

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Micro RNAs (miRNAs) are short non-coding RNAs (ncRNAs) of ~22 nucleotides in length involved in the post-transcriptional regulation of gene expression. They were discovered over 15 years ago and their functions are becoming clearer. They play an important role in all biological processes. MiRNAs are important modulators of the expression of eukaryotic genes. Focusing on transcripts encoding proteins they impact on the cellular transcriptome thus helping to determine the destiny of a cell. More and more data emerge to indicate an important functional role of miRNAs in the brain development. Since their discovery many miRNAs have been described as key factors in the development and function of the central nervous system. Some play a significant role in the genesis and differentiation of nerve cells (neurons and glial cells). Notably, it has recently been established that miRNAs play a vital role in the mechanisms underpinning the infantile increase of the gonadotropin-releasing hormone (GnRH) production by neurons in the hypothalamus. This phenomenon is necessary for the onset of puberty in mammals. In this review offers our attempt to describe miRNAs as new players in the control of hypothalamic functions, namely the onset of puberty.

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“…Notre capacité à répondre aux différents défis et aléas de la vie, aux facteurs de stress et au risque de maladie, pendant l'enfance et au cours de la vie adulte dépend du capital santé et du capital humain [1] dont nous sommes dotés à la naissance [59] (➜). Les notions selon lesquelles des mécanismes non génétiques et non culturels peuvent transmettre la mémoire des expositions à divers environnements et conditionner les réactions des géné-rations suivantes, sont à la base du concept des origines développementales de la santé et des maladies (DOHaD) et suscitent un intérêt grandissant [2].…”

Section: Les Théories De Jb Lamarck Revisitées à La Lumière De L'épunclassified

“…Pourtant, des études sur la drosophile ou le ver Caenorabditis elegans montrent qu'il existe bien dans certains cas une capacité d'adaptation, une résilience. La programmation peut conférer à des réseaux de gènes une capacité à répondre plus rapidement à un défi de l'environnement [59] (➜). De manière inattendue, il est éga-lement possible de constater dans la descendance des réponses différentes de celles observées sur le parent exposé.…”

Section: Les Théories De Jb Lamarck Revisitées à La Lumière De L'épunclassified

“…Un modèle intégrant ces différents systèmes de transmission, leurs interactions avec l'environnement ainsi que les fenêtres de sensibilité en fonction du sexe du parent et de l'enfant, reste à construire. < plus : la mère et le père (F0), leurs enfants (F1), et leurs petits enfants (F2), par des changements aux niveaux somatique et/ou germinal de la génération F1 (Figure 1) [59] (➜). Les expériences auxquelles l'individu est exposé in utero et au cours des 2 premières années (concept des 1 000 jours) représentent un indé-niable déterminant de son capital santé.…”

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