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Fetal myogenesis represents a critical period of porcine skeletal muscle development and requires coordinated expression of thousands of genes. Epigenetic mechanisms, including DNA methylation, drive transcriptional regulation during development; however, these processes are understudied in developing porcine tissues. We performed bisulfite sequencing to assess DNA methylation in pig longissimus dorsi muscle at 41- and 70-days gestation (dg), as well as RNA- and small RNA-sequencing to identify coordinated changes in methylation and expression between myogenic stages. We identified 45 739 differentially methylated regions (DMRs) between stages, and the majority (N = 34 232) were hypomethylated at 70 versus 41 dg. Integration of methylation and transcriptomic data revealed strong associations between differential gene methylation and expression. Differential miRNA methylation was significantly negatively correlated with abundance, and dynamic expression of assayed miRNAs persisted postnatally Motif analysis revealed significant enrichment of myogenic regulatory factor motifs among hypomethylated regions, suggesting that DNA hypomethylation may function to increase accessibility of muscle-specific transcription factors. We show that developmental DMRs are enriched for GWAS SNPs for muscle- and meat-related traits, demonstrating the potential for epigenetic processes to influence phenotypic diversity. Our results enhance understanding of DNA methylation dynamics of porcine myogenesis and reveal putative cis-regulatory elements governed by epigenetic processes. Key words: DNA methylation, pig, longissimus dorsi muscle, microRNA, WGBS, Introduction Skeletal muscle accounts for the majority of carcass weight in pigs and other livestock species, and its physiology influences numerous meat quality phenotypes (England et al. 2013). Fetal myogenesis [...]

MicroRNAs (miRNAs) are small, non-coding, regulatory RNAs that play important roles in abiotic stress responses in plants, but their regulatory roles in the adaptive response to heat stress at the booting stage in two rice varieties, 9311 and Nagina 22, remain largely unknown. In this study, 464 known miRNAs and 123 potential novel miRNAs were identified. Of these miRNAs, a total of 90 differentially expressed miRNAs were obtained with 9311 libraries as the control group, of which 54 were upregulated and 36 were downregulated. To gain insight into functional significance, 2773 potential target genes of these 90 differentially expressed miRNAs were predicted. GO enrichment analysis showed that the predicted target genes of differentially expressed miRNAs included NACs, LACs, CSD, and Hsp40. KEGG pathway analysis showed that the target genes of these differentially expressed miRNAs were significantly enriched in the plant hormone signal transduction pathway. The expression levels of 10 differentially expressed miRNAs and their target genes obtained by qRT-PCR were largely consistent with the sequencing results. This study lays a foundation for the elucidation of the miRNA-mediated regulatory mechanisms in rice at elevated temperatures. Key words: rice, heat-responsive, microRNA, target gene, booting stage, high-throughput sequencing. Les microARN (miARN) sont de petits ARN non-codants impliques dans la regulation genique et jouant des roles importants dans la reponse aux stress abiotiques chez les plantes. Cependant, leur role dans l'adaptation au stress thermique au stade de l'epiaison chez deux varietes de riz (9311 et Nagina 22) demeure largement inconnu. Dans ce travail, les auteurs ont identifie 464 miARN connus et 123 miARN potentiellement inedits. Parmi ces miARN, 90 ont presente une expression differentielle au sein d'une librairie ou 9311 etait employe comme temoin; 54 etant exprimes plus fortement et 36 plus faiblement. Pour jeter un eclairage sur leur signification fonctionnelle, les auteurs ont identifie 2773 genes potentiellement cibles par ces 90 miARN exprimes de maniere differentielle. Une analyse d'enrichissement GO a montre que les genes predits comme etant des cibles de ces miARN incluaient des NAC, LAC, CSD et Hsp40. Une analyse des sentiers KEGG a montre que le catalogue de genes-cibles etait significativement enrichi en genes impliques dans le sentier de transduction du signal des regulateurs de croissance. Les niveaux d'expression de 10 miARN exprimes de maniere differentielle et de leurs genes-cibles ont ete quantifies par qRT-PCR et les resultats etaient largement en accord avec les resultats du sequencage. Cette etude fournit une assise de connaissance pour elucider les mecanismes de regulation fondes sur les miARN qui sont en cause dans la reponse du riz aux temperatures elevees. [Traduit par la Redaction] Mots-cles : riz, thermosensible, microARN, gene-cible, stade de l'epiaison, sequencage a haut debit., Introduction Climate change is a severe challenge for global agriculture in the 21st century. According to the Intergovernmental Panel on Climate Change (IPCC 2013), the globally averaged combined land and [...]

The present study aims to explore the role of microRNA 145-5p (miR-145-5p) in hyperlipidemia. Using bioinformatics tools and a wide range of function and mechanism assays, we attempted to understand the specific function and potential mechanism of miR-145-5p in hyperlipidemia. A cholesterol-enriched diet induced an increase of serum cholesterol and triacylglycerol but a decrease of serum high-density lipoprotein. MiR-145-5p level was decreased in hyperlipidemia rat models. MiR-145-5p regulated lipid metabolism by antagonizing the alteration of high-density lipoprotein, cholesterol, and triacylglycerol in serum mediated by a cholesterol-enriched diet. In mechanism, miR-145-5p directly bound with p21 protein (RAC1)-activated kinase 7 (PAK7) and negatively regulated mRNA and protein levels of PAK7 in THP-1 cells. Furthermore, miR-145-5p level was negatively associated with PAK7 level in rat cardiac tissues. Finally, overexpression of PAK7 reversed the effects of miR-145-5p on [beta]-catenin activation and M2 macrophages polarization in THP-1 cells. In conclusion, MiR145-5p modulated lipid metabolism and M2 macrophage polarization by targeting PAK7 and regulating [beta]-catenin signaling in hyperlipidemia, which may provide a potential biomarker for the treatment of hyperlipidemia-induced cardiovascular diseases. Key words: miR-145-5p, PAK7, hyperlipidemia, [beta]-catenin signaling, M2 macrophage polarization. La presente etude vise a explorer le role du microARN 145-5p (miR-145-5p) dans l'hyperlipidemie. A l'aide d'outils bioinformatiques et d'un large eventail d'epreuves fonctionnelles et sur les modes d'action, nous avons tente de comprendre le fonctionnement specifique et le mode d'action eventuel du miR- 145-5p dans l'hyperlipidemie. Le regime alimentaire a teneur elevee en cholesterol a entraine une hausse du cholesterol total et du triacylglycerol seriques, mais un abaissement des lipoproteines de haute densite dans le serum. Le taux de miR-145-5p s'abaissait dans des modeles de rats en hyperlipidemie. Le miR-145-5p participait a la regulation du metabolisme lipidique par l'antagonisme des modifications apportees dans le serum aux lipoproteines de haute densite, au cholesterol et au triacylglycerol par un regime alimentaire a teneur elevee en cholesterol. Au point de vue des modes d'action, le miR-145-5p se liait directement a la PAK7 (proteine kinase activee par la proteine p21 (RAC1)) et assurait une regulation a la baisse des taux de PAK7 en ARNm et en proteines dans les cellules THP1. En outre, les taux de miR-145-5p etaient inversement proportionnels au taux de PAK7 dans les tissus cardiaques de rat. Enfin, la surexpression de la PAK7 entrainait une inversion des effets du miR-145-5p sur l'activation de la [beta]-catenine et la polarisation des macrophages M2 dans les cellules THP-1. En conclusion, le miR-145-5p participait a la modulation du metabolisme lipidique et a la polarisation des macrophages M2 en ciblant la PAK7 et en regulant la voie de signalisation de la [beta]-catenine dans l'hyperlipidemie, ce qui pourrait fournir un biomarqueur eventuel pour le traitement des maladies cardiovasculaires provoquees par l'hyperlipidemie. [Traduit par la Redaction] Mots-cles : miR-145-5p, PAK7, hyperlipidemie, voie de signalisation de la [beta]-catenine, polarisation des macrophages M2., Introduction In the recent decades, many modern technologies have been applied in the improvement of cardiovascular disorders (Phillips and Guazzi 2015; Van Camp 2014). However, cardiovascular diseases remain to be [...]

The objective was to identify the differential expressed miRNA during cerebral ischemia-reperfusion injury (CIRI) process, thereby assisting in elucidating the mechanism of CIRI development and providing a potential target for CIRI prevention and treatment. Six mice were randomly assigned to two groups: control group and CIRI model group. A global cerebral IR model by four-vessel occlusion was prepared among the CIRI model group. Brain tissues were collected 48 h after reperfusion. Total RNA was extracted for each sample. miRNA microarrays were employed to detect the differentially expressed miRNA between the CIRI group and the control group. One differentially expressed miRNA was selected for verification by PCR. Compared with the control group, 69 miRNAs were significantly differential expressed in samples of the CIRI group, among which 50 miRNAs were upregulated and 19 miRNAs were downregulated. The real-time qPCR results indicated that the results of the miRNA microarray were reliable. A number of miRNAs were significantly regulated in the CIRI model, which suggested that miRNA was closely associated with the pathological alterations after ischemia. These identified miRNAs may provide directions and targets for the future pathological research of CIRI. Key words: miRNA, CIRI, microarray, differential expression. Cette etude avait pour but de mettre en evidence le miARN exprime de facon differentielle au cours d'un processus de lesions d'ischemie-reperfusion cerebrales (LIRC), et donc de contribuer a elucider le mode d'action de la presentation de LIRC et de cerner des cibles eventuelles pour la prevention et le traitement des LIRC. Nous avons reparti aleatoirement six souris dans deux groupes : temoin et modele de LIRC. Nous avons prepare un modele d'IR cerebrale globale par l'occlusion de quatre vaisseaux dans le groupe LIRC. Nous avons preleve du tissu cerebral 48 h apres la reperfusion. Nous avons extrait de l'ARN total pour chaque echantillon. A l'aide de biopuces de miARN, nous avons tente de mettre en evidence le miARN exprime de facon differentielle entre les groupes LIRC et temoin. Nous avons selectionne un miARN exprime de maniere differentielle aux fins de verification par PCR. Comparativement au groupe temoin, 69 miARN s'exprimaient de maniere differentielle de facon notable dans les echantillons du groupe LIRC, parmi lesquels 50 miARN etaient regules a la hausse et 19 miARN etaient regules a la baisse. Les donnees de PCR quantitatif en temps reel ont montre que les resultats obtenus a l'aide de la biopuce de miARN pouvaient etre consideres comme etant fiables. En conclusion, un certain nombre de miARN etaient regules de facon notable dans un modele de LIRC, ce qui laissait entendre que le miARN serait associe de pres aux modifications pathologiques observees apres une ischemie. Les miARN ainsi mis en evidence pourraient permettre d'obtenir des avenues et des cibles pour des recherches futures de pathologie portant sur les LIRC. [Traduit par la Redaction] Mots-cles: miARN, lesions d'ischemie-reperfusion cerebrales, biopuce, expression differentielle., Introduction Cerebral vascular disease is one of the three major diseases worldwide among which ischemic cerebrovascular disease accounts for 80%-85%, and its mortality rate ranks second among human diseases (Lopez [...]

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related deaths worldwide, especially in developing countries. Although advances in surgical procedures and targeted medicine have improved the overall survival of patients with HCC, the prognosis is poor. Hence, there is a need to identify novel therapeutic targets for HCC. Here, we report that the expression of RP11-909N17.2, a novel, long, noncoding RNA (lncRNA), is dysregulated in patients with HCC and cell lines. Additionally, this study demonstrated that RP11-909N17.2 facilitates the proliferation and invasion of HCC cells by binding to miRNA-767-3p, a tumor-suppressive microRNA (miRNA). Small integral membrane protein 7 (SMIM7) was identified as the downstream target of miRNA-767-3p. The expression of SMIM7 was upregulated in HCC clinical samples and cell lines. Moreover, SMIM7 was involved in the proliferation and invasion of HCC cells. Furthermore, SMIM7 inhibited the apoptosis of HCC cells, which indicated the oncogenic role of SMIM7 in HCC. The findings of this study suggest that the lncRNA-miRNA-mRNA regulatory axis, which regulates the pathogenesis of HCC, can be a potential novel diagnostic and therapeutic target for HCC. Key words: long noncoding RNA, miRNA-767-3p, hepatocellular carcinoma, proliferation, SMIM7. Le carcinome hepatocellular (CHC) est l'une des causes les plus frequentes de deces lies au cancer a travers le monde, particulierement dans les pays en developpement. Malgre les progres realises dans les procedures chirurgicales et en medecine ciblee qui ont ameliore la survie globale des patients atteints de CHC, le pronostic est mauvais. Il est donc necessaire d'identifier de nouvelles cibles therapeutiques du CHC. L'equipe de recherche rapporte ici que l'expression du RP11-909N17.2, un nouvel ARN long non codant (ARNlnc), est deregulee chez les patients atteints de CHC et dans les lignees cellulaires. En outre, cette etude a demontre que le RP11-909N17.2 facilite la proliferation et l'invasion des cellules de CHC en se liant au miRNA-767-3p, un microARN (miARN) suppresseur tumoral. La petite proteine membranaire integrale 7 (SMIM7) a ete identifiee comme cible en aval du miRNA-767-3p. L'expression de SMIM7 etait regulee a la hausse dans les echantillons cliniques et les lignees cellulaires de CHC. Par ailleurs, SMIM7 etait impliquee dans la proliferation et l'invasion des cellules de CHC. Qui plus est, SMIM7 inhibait l'apoptose des cellules de CHC, ce qui indiquait que SMIM7 joue un role oncogene dans le CHC. Les resultats de cette etude suggerent que l'axe regulateur ARNlnc-miARN-ARNm, qui regule la pathogenese du CHC, peut constituer une nouvelle cible diagnostique et therapeutique potentielle dans le CHC. [Traduit par la Redaction] Mots-cles: ARN long non codant, miRNA-767-3p, carcinome hepatocellulaire, proliferation, SMIM7., Introduction Hepatocellular carcinoma (HCC), the second most common cause of cancer-related deaths worldwide, is common in developing countries due to the prevalence of infections, such as hepatitis B virus infection [...]

Glioma is one of the most common and aggressive malignant primary brain tumors, with a poor 5-year survival rate. The long noncoding RNA (lncRNA) CTBP1-AS2 has been shown to be correlated with the prognosis of cancer, but the role of CTBP1-AS2 in glioma and its concrete mechanism is fully unknown. The clinical data and tissues of glioma patients were analyzed. Cell viability and migration assays were performed. Western blotting and qRT-PCR were adopted for investigation of target protein expressions. Double luciferase assay was used to investigate the interaction between different elements. The lncRNA CTBP1-AS2 had increased expression profiles in tumor tissues, which is associated with poor prognosis. In detail, CTBP1-AS2 knockdown decreased proliferation and migration phenotypes in both U87-MG and LN229 cells. Moreover, CTBP1-AS2 knockdown suppressed the key epithelial-mesenchymal transition (EMT) markers by downregulating Wnt7a-mediated signaling. Furthermore, miR-370-3p functioned as a link that could be absorbed by CTBP1-AS2, thus regulating Wnt7a expression. Lastly, the CTBP1-AS2--miR-370-3p--Wnt7a axis modulated EMT in glioma cells in vitro and in vivo. This study provides new insights that a novel lncRNA, CTBP1-AS2, regulates EMT of glioma by modulating the miR-370-3p-Wnt7a axis. Key words: CTBP1-AS2, miR-370-3p, Wnt7a, epithelial--mesenchymal transition, glioma. Le gliome est l'une de tumeurs cerebrales primaires malignes les plus frequentes et les plus agressives, avec un faible taux de survie apres 5 ans. S'avere que le long ARNnc CTBP1-AS2 est correle au pronostic du cancer, mais le role du CTBP1-AS2 dans le gliome et son mecanisme concret d'action sont totalement inconnus. Les donnees cliniques et les tissus des patients atteints de gliome ont ete analyses. Des tests de viabilite et de migration cellulaire ont ete realises. Le buvardage Western et la qRT-PCR ont ete retenus pour examiner l'expression de proteines cibles. Le dosage d'un rapporteur double luciferase a ete utilise pour examiner l'interaction entre differents elements. Le long ARNnc CTBP1-AS2 presentait des profils d'expression accrue dans les tissus tumoraux, ce qui est associe a un mauvais pronostic. En detail, le knockdown de CTBP1-AS2 diminuait la proliferation et la migration des cellules U87-MG et LN229. De plus, le knockdown de CTBP1-AS2 reprimait l'expression des principaux marqueurs de la transition epithelio--mesenchymateuse (TEM) en regulant a la baisse la signalisation mediee par Wnt7a. Par ailleurs, le miR-370-3p agissait comme lien qui pouvait etre capte par le CTBP1-AS2, regulant ainsi l'expression de Wnt7a. Finalement, l'axe CTBP1-AS2--miR-370-3p--Wnt7a modulait la TEM dans les cellules de gliome in vitro et in vivo. Cette etude apporte des connaissances originales sur le fait qu'un long ARNnc nouveau, le CTBP1-AS2, regule la TEM du gliome en modulant l'axe miR-370-3p--Wnt7a. [Traduit par la Redaction] Mots-cles: CTBP1-AS2, miR-370-3p, Wnt7a, transition epithelio--mesenchymateuse, gliome., Introduction Brain and other central nervous system (CNS) tumors (both malignant and nonmalignant) are the most common cancer site in persons age 0-14 years, with an average annual age-adjusted incidence [...]

Dormancy is evolutionarily widespread and can take many forms, including diapause, dauer formation, estivation, and hibernation. Each type of dormancy is characterized by distinct features; but accumulating evidence suggests that each is regulated by some common processes, often referred to as a common 'toolkit' of regulatory mechanisms, that likely include noncoding RNAs that regulate gene expression. Non-coding RNAs, especially microRNAs, are well-known regulators of biological processes associated with numerous dormancy-related processes, including cell cycle progression, cell growth and proliferation, developmental timing, metabolism, and environmental stress tolerance. This review provides a summary of our current understanding of noncoding RNAs and their involvement in regulating dormancy., Introduction Becoming dormant provides a means to survive changing environments and inhospitable conditions. Dormancy is widespread across all animal phyla, ranging from sponges to mammals; and it can take a [...]

Stress responses are important to human physiology and pathology, and the inability to adapt to cellular stress leads to cell death. To mitigate cellular stress and re-establish homeostasis, cells, including those in the cardiovascular system, activate stress coping response mechanisms. The endoplasmic reticulum, a component of the cellular reticular network in cardiac cells, mobilizes so-called endoplasmic reticulum stress coping responses, such as the unfolded protein response. MicroRNAs play an important part in the maintenance of cellular and tissue homeostasis, perform a central role in the biology of the cardiac myocyte, and are involved in pathological cardiac function and remodeling. In this paper, we review a link between endoplasmic reticulum homeostasis and microRNA with an emphasis on the impact on stress responses in the cardiovascular system. Key words: ER stress, microRNA, unfolded protein response, endoplasmic reticulum, heart. Les reactions au stress sont importantes en physiologie et en pathologie humaines, et l'incapacite de s'adapter au stress cellulaire mene a la mort de cellules. Afin d'attenuer le stress cellulaire et de retablir l'homeostasie, les cellules, y compris celles du systeme cardiovasculaire, entrainent l'activation de modes d'action de reactions adaptatives au stress. Le reticulum endosplasmique, une composante du reseau reticulaire cellulaire dans les cellules cardiaques, mobilise ce que l'on appelle des reactions adaptatives au stress du reticulum endosplasmique, comme la reponse UPR (pour<< unfolded protein response >>). Les microRNA jouent un role important dans le maintien de l'homeostasie cellulaire et tissulaire, un role central dans la biologie du cardiomyocyte et participent au fonctionnement cardiaque pathologique et au remodelage. Dans cet article, nous etudions un lien entre l'homeostasie du reticulum endoplasmique et les microRNA en mettant l'emphase sur leur incidence sur les reactions au stress dans le systeme cardiovasculaire. [Traduit par la Redaction] Mots-cles: stress du RE, microRNA, reponse UPR, reticulum endoplasmique, creur., Introduction Stress responses are central to human physiology and pathology, and failure to adapt to cellular stress leads to cell death. To mitigate cellular stress and re-establish homeostasis, cardiac cells [...]

Myostatin (MSTN) is a key muscle factor that negatively regulates skeletal muscle growth and development. Our laboratory recently produced genetically engineered Meishan pigs containing a ZFN-edited MSTN loss-of-function mutation (MSTN-/-, MKO) that led to the hypertrophy of skeletal muscles. In this study, we performed transcriptome sequencing and miRNA sequencing in skeletal muscle samples from MKO and wildtype Meishan (MWT) pigs to investigate the effect of MSTN-/- on expression of mRNA and miRNA. Our results indicated that, compared to MWT pigs, there were 200 genes and 4 miRNAs being significantly up-regulated, and 238 genes and 5 miRNAs being significantly down-regulated in MKO pigs. Analysis by GO and KEGG pathways revealed that differentially expressed miRNAs and their target genes of those differentially expressed miRNAs were involved in the signal pathways of skeletal muscle growth and development such as AMPK, mTOR, and TGF-beta. An integrated analysis of the correlation between miRNA-mRNA and transcriptome predicated that XK and METTL8 were target genes for miR-499-5p, while LRP4 was a target gene for miR-490-3p. Our results provide important clues to help us further investigate MSTN's regulatory mechanisms during skeletal muscle growth and development. Key words: myostatin, transcriptome sequencing, miRNA sequencing, integrated analysis, Meishan pigs. La myostatine (MSTN) est un facteur cle qui regule negativement la croissance et le developpement des muscles squelettiques. Le laboratoire des auteurs a recemment produit des porcs Meishan modifies genetiquement contenant une mutation nulle (MSTN-/-, MKO) du gene de la myostatine, obtenue par edition genomique a l'aide d'une nuclease ZFN. Cette mutation a entraine une hypertrophie des muscles squelettiques. Dans ce travail, les auteurs ont sequence le transcriptome et les miARN au sein d'echantillons de muscles provenant de porcs Meishan MKO et de type sauvage (MWT) pour etudier les effets de la mutation nulle sur l'expression des ARNm et les miARN. Les resultats obtenus indiquent que, compare au type sauvage, 200 genes et 4 miARN etaient exprimes significativement plus fortement, tandis que 238 genes et 5 miARN etaient exprimes significativement moins que chez les porcs MWT. Une analyse des annotations GO et des sentiers KEGG a revele que les miARN qui sont exprimes de maniere differentielle et les genes cibles par ces memes miARN seraient impliques dans les voies de signalisation de la croissance et du developpement des muscles squelettiques telles que AMPK, mTOR et TGF-beta. Une analyse conjointe de la correlation entre les miARN-ARNm et le transcriptome a permis de predire que les genes XK et METTL8 etaient cibles par le miR-499-5p, tandis que le gene LRP4 etait une cible de miR-490-3p. Ces resultats fournissent des indices importants pour aider a etudier les mecanismes de regulation medies par la myostatine au cours de la croissance et du developpement des muscles. [Traduit par la Redaction] Mots-cles : myostatine, sequencage du transcriptome, sequencage des miARN, analyse conjointe, porcs Meishan., Introduction Myostatin (MSTN) is a transcriptional growth factor belonging to the transforming growth factor beta (TGF[beta]) superfamily, and its main function is to negatively regulate skeletal muscle growth and development. [...]

Cardiac fibrosis, characterized by excessive accumulation of extracellular matrix, abolishes cardiac contractility, impairs cardiac function, and ultimately leads to heart failure. In recent years, significant evidence has emerged that supports the highly dynamic and responsive nature of the cardiac extracellular matrix. Although our knowledge of cardiac fibrosis has advanced tremendously over the past decade, there is still a lack of specific therapies owing to an incomplete understanding of the disease etiology and process. In this review, we attempt to highlight some of the recently investigated molecular determinants of ischemic and non-ischemic fibrotic remodeling of the myocardium that present as promising avenues for development of anti-fibrotic therapies. Key words: cardiac fibrosis, transcription factors, histone deacetylases, transforming growth factor beta, microRNA. La fibrose cardiaque, caracterisee par une accumulation excessive de matrice extracellulaire, empeche la contractilite du coeur, nuit a la fonction cardiaque et mene ultimement a l'insuffisance cardiaque. Au cours des dernieres annees, bien des donnees probantes ont emerge a l'appui de la nature tres dynamique et reactive de la matrice extracellulaire cardiaque. Meme si nos connaissances sur la fibrose cardiaque ont enormement evolue au cours des dix dernieres annees, on manque toujours de traitements specifiques en raison d'une comprehension incomplete de l'etiologie et des processus de la maladie. Dans cet article de synthese, nous tentons de mettre en lumiere certains des determinants moleculaires du remodelage fibrotique du myocarde ischemique et non ischemique qui ont ete etudies recemment et qui menent vers des avenues prometteuses quant au developpement de traitements contre la fibrose. [Traduit par la Redaction] Mots-cles : fibrose cardiaque, facteurs de transcription, histone desacetylases, facteur de croissance transformant beta, micro ARN., Introduction Cardiac fibrosis is a pathological condition that ensues following acute cardiac injuries like myocardial infarction (MI) and chronic conditions like hypertension and valvular disease (Kong et al. 2014; Weber [...]

During the pathogenetic process of varied kidney diseases, renal tubules are the major sites in response to detrimental insults, including pro-inflammatory stimuli. MicroRNA-204-5p (miR-204-5p) can be detected in the renal tubular epithelial cells in the normal kidney; its expression, however, is downregulated in the kidney with pathological changes. This study aimed to investigate the role of miR-204-5p in interleukin 6 (IL6) mediated inflammatory response and chemokine production in HK-2 renal tubular cells. In HK-2 cells, the expression of miR-204-5p was downregulated in response to exogenous pro-inflammatory stimulus, tumor necrosis factor [alpha] (TNF[alpha]), or IL1[beta], while that of IL6 receptor [alpha] (IL6R) was upregulated. Dual-luciferase results confirmed that miRNA-204-5p directly targeted IL6R. In addition to suppressing IL6R expression, miRNA-204-5p agomir also inhibited the phosphorylation of signal transducer and activator of transcription 3 (STAT3) in HK-2 cells exposed to exogenous IL6. Further, miRNA-204-5p suppressed the overproduction of pro-inflammatory mediators (cyclooxygenase 2 and prostaglandin [E.sub.2]) and chemokines (C-C motif chemokine ligand 2 and C-X-C motif chemokine ligand 8). The anti-inflammatory effects of miRNA-204-5p were attenuated when IL6R was reexpressed in HK-2 cells. Collectively, our study reveals that miR-204-5p inhibits the inflammation and chemokine generation in renal tubular epithelial cells by modulating the IL6/IL6R axis. Key words: microRNA-204-5p, IL6R, renal tubular epithelial cells, inflammation, chemokine generation. Durant le processus pathogenique qui mene au developpement de diverses maladies renales, les tubules sont les principaux sites endommages par differentes agressions, y compris par les stimulus pro-inflammatoires. Le microARN-204-5p (miR-204-5p) peut etre detecte dans les cellules epitheliales tubulaires renales du rein normal, mais son expression est toutefois regulee a la baisse dans le rein pathologique. Cette etude visait a examiner le role du miR-204-5p sur la reponse inflammatoire mediee par l'interleukine-6 (IL6) et la production de chimiokines chez les cellules tubulaires renales HK-2. L'expression du miR-204-5p etait regulee a la baisse dans ces cellules en reponse a un stimulus pro-inflammatoire exogene, soit le facteur de necrose tumorale [alpha] (TNF[alpha]) ou l'IL1[beta], alors que le recepteur de l'IL6 [alpha] (IL6R) etait regule a la hausse. Les resultats d'un dosage double de la luciferase confirmaient que le miR-204-5p ciblait directement l'IL6R. En plus de supprimer l'expression de l'IL6R, un miR-204-5p synthetique (agomir) inhibait aussi la phosphorylation de STAT3 chez les cellules HK-2 exposees a l'IL6 exogene. En outre, le miR-204-5p supprimait la surproduction de mediateurs (cyclooxygenase 2 et prostaglandine E2) et de chimiokines (CCL2 et CXCL8) pro-inflammatoires. Les effets anti-inflammatoires du miR-204-5p etaient attenues lorsque l'IL6R etait reexprime dans les cellules HK-2. Dans son ensemble, l'etude des auteurs revele que le miR-204-5p inhibe l'inflammation et la production de chimiokines dans les cellules epitheliales tubulaires renales en modulant l'axe IL6/IL6R. [Traduit par la Redaction] Mots-cles: microARN-204-5p, IL6R, cellules epitheliales tubulaires renales, inflammation, production de chimiokine., Introduction MicroRNAs (miRNAs) are a group of small noncoding RNAs (19-23 nt) that regulate gene expression. As epigenetic regulators, miRNAs participate not only in the development and homeostasis of the [...]