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Localization of microRNA-375 in perinatal rat pancreas 微rna -375在围产期大鼠胰腺中的定位
Pub Date : 2018-08-01 DOI: 10.1515/micrnado-2018-0001
Louise Larsen, M. Rosenstierne, J. Nielsen, L. Dalgaard
Abstract MicroRNA (miRNA)-375 is highly expressed in the pancreatic endocrine islets. Maintaining appropriate miR-375 levels is very important for beta cell development, function and proliferation. The aim of the current study was to investigate the regulation and localization of miR-375 in rat perinatal pancreas at embryonic day 20 (E20), postnatal day 0 (D0) and day 2 (D2). Expression levels of miR-375 were measured by in situ hybridization on fixed neonatal rat pancreas. Interestingly, while miR-375 was detectable at robust levels at all three time points, the major site of expression of miR-375 at D0 and D2 was in pancreatic exocrine cells. Our data show that miR-375 has a dynamic change of expression in pancreatic exocrine tissue during the perinatal period. Moreover, these findings indicate that pancreatic endocrine cells may not always be the major source of expression of miR-375 in pancreas. We suggest that the marked change of miR-375 levels in exocrine cells following birth could regulate processes involved in the adaptation of the exocrine pancreas to digestion of external nutrients derived from milk.
MicroRNA (miRNA)-375在胰腺内分泌胰岛中高表达。维持适当的miR-375水平对β细胞的发育、功能和增殖非常重要。本研究的目的是研究miR-375在大鼠胚胎第20天(E20)、出生后第0天(D0)和第2天(D2)围产儿胰腺中的调控和定位。通过原位杂交检测miR-375在固定新生大鼠胰腺上的表达水平。有趣的是,虽然在所有三个时间点都可以检测到miR-375的强劲水平,但在D0和D2时,miR-375的主要表达位点是在胰腺外分泌细胞中。我们的数据显示,miR-375在围产期胰腺外分泌组织中的表达发生了动态变化。此外,这些发现表明胰腺内分泌细胞可能并不总是胰腺中miR-375表达的主要来源。我们认为,出生后外分泌细胞中miR-375水平的显著变化可能调节外分泌胰腺对来自牛奶的外部营养物质消化的适应过程。
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引用次数: 1
The long noncoding RNA Bsr in the genomically imprinted Dlk1-Dio3 region is suppressed in newborn rat pancreas by gestational obesity 妊娠肥胖抑制新生大鼠胰腺基因组印迹Dlk1-Dio3区域的长链非编码RNA Bsr
Pub Date : 2018-08-01 DOI: 10.1515/micrnado-2018-0002
Caroline Jaksch, I. Iessi, P. Thams, S. Poulsen, B. Levin, L. Dalgaard, J. Nielsen
Abstract Background: Fetal metabolic programming imposed by maternal obesity and impaired glucose tolerance predisposes the offspring to metabolic disease and beta cell dysfunction as adults. The aim of this study was to assess the whole pancreas RNA changes in neonatal offspring exposed to fetal programming. Methods: The outcome of fetal programming on offspring was tested using the selectively bred Diet Induced Obese (DIO) and the Diet Resistant (DR) strains. DIO and DR rats were fed either chow or high fat, high sucrose (high energy, HE) diet during gestation and the differences in pancreas RNA expression at two days after birth were measured by microarray. Pancreas sections were stained and analyzed for alpha and beta cell numbers. Neonatal islets were treated with cytotoxic cytokines and RNA measured by RT-Q-PCR. Results: Morphometric analyses revealed significant differences in alpha and beta cell numbers per pancreas or per islet by HE diet. Microarray analyses revealed 11 fold downregulation of the long noncoding RNA Bsr in whole pancreas by HE feeding of DIO rat dams. MicroRNAs from the same locus, the Dlk1- Dio3 imprinted region, were also decreased by HE diet. Moreover, treatment of isolated neonatal islets with inflammatory cytokines, IL-1β and IFN-γ, led to reduction of Bsr transcript in a time and dose dependent manner. Conclusions: Our data suggest that fetal programming of Bsr may play a role in beta cell dysfunction in obesity and type 2 diabetes.
背景:母体肥胖和糖耐量受损导致的胎儿代谢编程使后代成年后易患代谢疾病和β细胞功能障碍。本研究的目的是评估暴露于胎儿编程的新生儿全胰腺RNA的变化。方法:采用选择性饲养的饮食诱导肥胖(DIO)和饮食耐药(DR)品系,对子代进行胎儿计划育的结果进行试验。妊娠期分别饲喂高脂、高糖(高能量,HE)日粮和低脂、高糖日粮,出生后第2天用微阵列检测胰腺RNA表达差异。胰腺切片染色并分析α和β细胞数量。用RT-Q-PCR法测定新生儿胰岛细胞毒性细胞因子和RNA。结果:形态计量学分析显示,HE饮食对每个胰腺或每个胰岛的α和β细胞数量有显著差异。微阵列分析显示,HE喂养DIO大鼠全胰腺长链非编码RNA Bsr下调了11倍。来自同一位点Dlk1- Dio3印迹区的microrna也被HE饮食减少。此外,用炎性细胞因子IL-1β和IFN-γ治疗离体新生儿胰岛,可导致Bsr转录减少,并呈时间和剂量依赖性。结论:我们的数据表明胎儿Bsr编程可能在肥胖和2型糖尿病的β细胞功能障碍中起作用。
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引用次数: 1
Commentary: Cross-talks between microbiota and microRNAs 评论:微生物群和microrna之间的交叉对话
Pub Date : 2017-01-11 DOI: 10.1515/micrnado-2017-0001
Holly Kristensen-Walker
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引用次数: 0
Combined Immuno-FISH confirms islet-specific miRNAs 联合免疫- fish确认胰岛特异性mirna
Pub Date : 2017-01-11 DOI: 10.1515/micrnado-2017-0002
Wilson K. M. Wong, Malati R. Umrani, M. Joglekar
Abstract Combined immuno-FISH offers an important tool for understanding the localization of mature microRNAs with reference to other proteins within the same cell. This procedure has been previously demonstrated by our team and the method has been described earlier [1, 2].
联合免疫- fish为了解成熟microrna与同一细胞内其他蛋白的定位提供了重要工具。我们的团队之前已经演示过这个过程,并且该方法已经在前面描述过[1,2]。
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引用次数: 0
Role of miR-200a in regulating the insulin signalling in the hypothalamus miR-200a在调节下丘脑胰岛素信号传导中的作用
Pub Date : 2014-09-19 DOI: 10.2478/micrnado-2014-0003
Poonam R. Pandey, V. Seshadri
Leptin and Insulin mediated signalling have been known to play a significant role in energy utilization and body weight. Obese mice with leptin mutations were known to have several impairments but the contribution of micro RNA to the manifestation of these impairments in the Ob/ Ob mice (lacking functional leptin) were not explored in detail. miRNA play an important role in regulating obesity was indicated by the obese phenotype of the mice lacking Dicer in the PMOC neuron [1]. Leptin is an essential neurotrophic factor in early development and also reduced Leptin during early development results in obesity, thus it can be hypothesized that some of the effects of the leptin deprivation could be mediated by miRNAs. Recently Crepin and co-workers have studied differential expression of micro RNAs in the hypothalamus of the Ob/Ob mice compared to control mice [2]. In the initial screen using Taqman Low Density assay (TLDA) array they identified eleven miRNA’s that are differentially expressed and three of these miRNA (miR-200a, miR-200b and miR-429) were further analysed by quantitative PCR to confirm their over expression in Ob/Ob mice. Further, the authors have demonstrated that leptin treatment in ob/ob mice reduces the expression of miR-200a, miR-200b and miR-429 when compared to the vehicle control. miR200a was also shown to be upregulated in the db/db mice (lacking functional leptin receptors). IRS2 and Leptin receptor (ObRb) mRNA were identified as functional target of miR-200a. Using luciferase reporter assay they, have demonstrated that miR-200a targets the 3’UTR region of insulin receptor substrate 2 (IRS2) and leptin receptor (ObRb) in CHO cells. Interestingly, Commentary
已知瘦素和胰岛素介导的信号传导在能量利用和体重中起重要作用。已知瘦素突变的肥胖小鼠有几种损伤,但微RNA在Ob/ Ob小鼠(缺乏功能性瘦素)中对这些损伤的表现的贡献尚未得到详细探讨。PMOC神经元缺乏Dicer小鼠的肥胖表型表明miRNA在调节肥胖中发挥重要作用[1]。瘦素是早期发育中必不可少的神经营养因子,而在发育早期瘦素的减少也会导致肥胖,因此可以假设,瘦素剥夺的一些影响可能是由mirna介导的。最近Crepin和同事研究了Ob/Ob小鼠下丘脑中微rna与对照小鼠的差异表达[2]。在使用Taqman低密度测定(TLDA)阵列的初始筛选中,他们鉴定出11个差异表达的miRNA,并通过定量PCR进一步分析其中3个miRNA (miR-200a, miR-200b和miR-429),以确认它们在Ob/Ob小鼠中的过表达。此外,作者已经证明,与载体对照相比,瘦素治疗ob/ob小鼠降低了miR-200a, miR-200b和miR-429的表达。miR200a在db/db小鼠(缺乏功能性瘦素受体)中也被显示上调。IRS2和瘦素受体(ObRb) mRNA被确定为miR-200a的功能靶点。通过荧光素酶报告基因测定,他们已经证明miR-200a靶向CHO细胞中胰岛素受体底物2 (IRS2)和瘦素受体(ObRb)的3'UTR区域。有趣的是,评论
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引用次数: 2
MicroRNAs in diabetes - are they perpetrators in disguise or just epiphenomena?
Pub Date : 2014-09-19 DOI: 10.2478/micrnado-2014-0002
P. Puthanveetil, Anu Thomas, S. Chakrabarti
Abstract MicroRNAs (miRNA) are non-coding RNAs, the majority of which are 22 nucleotide in size. They regulate gene transcription and control more than 50% of the mammalian genome. Although functional significance and targets of several miRNAs are yet to be identified, they may be regarded as controller of cellular physiology and function. Through such regulation they play vital roles in normal and diseased states. In the context of diabetes and chronic diabetic complications, recent research has identified alterations of a significant number of miRNAs. However, in a complex chronic disease like diabetes, multiple transcripts may also change in a temporal fashion depending on the disease progression and activation of counter-regulatory mechanisms. Hence, it is also possible that some miRNA changes may not be causally related to the disease pathogenesis and represent epiphenomena. To date, over 500 studies have addressed the role of miRNAs in the pathogenesis of type 1 and type 2 diabetes and chronic diabetic complications. Majority of the altered miRNAs appear to have pathogenetic roles. In this review, we have tried to identify alterations of specific miRNAs and the pathways they may regulate. We have also tried to identify whether some of these miRNA alterations may form basis of potential treatments
MicroRNAs (miRNA)是一种非编码rna,大多数大小为22个核苷酸。它们调节基因转录并控制超过50%的哺乳动物基因组。虽然一些mirna的功能意义和靶点尚未确定,但它们可能被认为是细胞生理和功能的控制者。通过这种调节,它们在正常和患病状态中起着至关重要的作用。在糖尿病和慢性糖尿病并发症的背景下,最近的研究已经发现了大量mirna的改变。然而,在像糖尿病这样复杂的慢性疾病中,多种转录本也可能在时间上发生变化,这取决于疾病的进展和反调控机制的激活。因此,也有可能一些miRNA的变化与疾病的发病机制没有因果关系,只是一种附带现象。迄今为止,已有超过500项研究探讨了mirna在1型和2型糖尿病及慢性糖尿病并发症发病机制中的作用。大多数改变的mirna似乎具有致病作用。在这篇综述中,我们试图确定特定mirna的改变及其可能调节的途径。我们还试图确定这些miRNA的改变是否可能构成潜在治疗的基础
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引用次数: 2
MicroRNAs: emerging regulators for development of pancreatic islet lineages microrna:胰岛谱系发展的新兴调控因子
Pub Date : 2014-07-26 DOI: 10.2478/micrnado-2013-0002
F. Jiang, G. Morahan
Abstract MicroRNAs belong to a family of small (-23 nt) non-coding RNAs that mediate posttranscriptional gene silencing. They are emerging as important new regulators of differentiation and development. Knowledge of their role in pancreas and islet development, may help in developing a regenerative therapy for diabetes mellitus, a metabolic disorder affecting hundreds of millions of people worldwide. In this minireview, we summarize the latest evidence of the role these new regulators play in islet lineage development, aiming to attract more research into this important developmental regulators.
MicroRNAs属于介导转录后基因沉默的小(- 23nt)非编码rna家族。它们正在成为差异化和发展的重要新监管者。了解它们在胰腺和胰岛发育中的作用,可能有助于开发糖尿病的再生疗法,糖尿病是一种影响全球数亿人的代谢紊乱。在这篇综述中,我们总结了这些新的调节因子在胰岛谱系发育中所起作用的最新证据,旨在吸引更多对这一重要发育调节因子的研究。
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引用次数: 0
Identification of a novel miRNA targeting CD146 for suppression of angiogenesis 靶向CD146抑制血管生成的新型miRNA的鉴定
Pub Date : 2014-07-01 DOI: 10.2478/micrnado-2014-0001
S. Chung, Weiyong Shen, M. Gillies
Abstract Angiogenesis is the pathological process of forming new blood vessels from pre-existing vessels. It is one of the main features of many conditions such as cancer and inflammatory diseases. MicroRNAs (miRNAs) are small non-coding RNAs that regulate post-transcriptional gene expression. Recent studies have suggested that miRNAs play a significant role in angiogenesis. The study from Wang et al reported a novel angiomiR, miRNA-329, and its negative correlation with CD 146 expression in angiogenesis. These in vitro and in vivo studies introduce an appealing new way of treating angiogenesis by targeting CD146.
血管生成是指原有血管形成新血管的病理过程。它是许多疾病的主要特征之一,如癌症和炎症性疾病。MicroRNAs (miRNAs)是调节转录后基因表达的小非编码rna。最近的研究表明,mirna在血管生成中起着重要作用。Wang等人的研究报告了一种新的血管组ir miRNA-329,其在血管生成过程中与cd146的表达呈负相关。这些体外和体内研究介绍了一种靶向CD146治疗血管生成的新方法。
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引用次数: 0
MicroRNAs and pancreatic-endocrine system microrna与胰腺内分泌系统
Pub Date : 2014-07-01 DOI: 10.2478/micrnado-2013-0003
E. Luzi, F. D’Asta, M. Brandi
Abstract MicroRNAs (miRNAs) are endogenous single-stranded non-coding RNAs of about - 22 nucleotides which suppress gene expression by selectively binding to the 3’ non coding region (3’-UTR) of specific messenger RNAs through base-pairing. There are now more than 1600 human miRNAs annotated in the miRNA registry (http://microrna.sanger.ac.uk), but, at the moment, very few miRNAs have been well characterized and most of their roles remain unknown. miRNAs derive from transcripts that fold back on themselves to form distinctive hairpin structures, whereas the other types of endogenous small RNAs derive either from much longer hairpins that give rise to a greater diversity of small RNAs (siRNAs), or from bimolecular RNA duplexes (siRNAs), or from precursors without any suspected doublestranded character (piRNAs). The key step to understanding more about the possible functions of microRNA is to identify their mRNA targets. Recent studies have supported a role of miRNAs in the initiation and progression of human malignancies. Several groups have studied the global miRNA expression in cancer patients and found that miRNAs show different patterns of expression in normal and tumor tissues. The involvement of miRNAs in human cancer is probably due to the fact that >50% of miRNA genes are located at chromosomal regions, such as fragile sites or common break point sites, and regions of deletion or amplification that are generally altered in human tumors. Experimental evidence has shown that miRNA expression profiles enable the classification of poorly characterized human tumors that cannot be accurately classified using only the mRNA expression patterns. As a result, the miRs involved in the oncogenic transformation process are being investigated as novel biomarkers of disease detection and prognosis as well as potential therapeutic targets for human cancers. The aim of this review is to provide a general background regarding current knowledge about miRNA involvement in human pancreatic cancer and in the regulation of glucose metabolism.
MicroRNAs (miRNAs)是一种内源性单链非编码rna,长度约为- 22个核苷酸,通过碱基配对选择性结合特异性信使rna的3 '非编码区(3 ' - utr),抑制基因表达。目前,在miRNA注册表中有超过1600种人类miRNA被注释(http://microrna.sanger.ac.uk),但是,目前,很少有miRNA被很好地表征,而且它们的大多数作用仍然未知。mirna来源于自身折叠形成独特的发夹结构的转录本,而其他类型的内源性小RNA来源于产生更大多样性的小RNA (sirna)的更长的发夹,或者来自双分子RNA (sirna),或者来自没有任何可疑双链特征的前体(piRNAs)。进一步了解microRNA可能功能的关键一步是确定它们的mRNA靶标。最近的研究支持mirna在人类恶性肿瘤的发生和发展中的作用。多个研究小组研究了肿瘤患者miRNA的全局表达,发现miRNA在正常组织和肿瘤组织中表现出不同的表达模式。miRNA参与人类癌症可能是由于50%的miRNA基因位于染色体区域,如脆弱位点或共同断点位点,以及在人类肿瘤中通常发生改变的缺失或扩增区域。实验证据表明,miRNA表达谱能够对仅使用mRNA表达模式无法准确分类的特征较差的人类肿瘤进行分类。因此,参与致癌转化过程的miRs正在作为疾病检测和预后的新型生物标志物以及人类癌症的潜在治疗靶点进行研究。这篇综述的目的是为目前关于miRNA参与人类胰腺癌和葡萄糖代谢调节的知识提供一个总的背景。
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引用次数: 2
From Cradle to the Grave: Tissue-specific microRNA signatures in detecting clinical progression of diabetes 从摇篮到坟墓:检测糖尿病临床进展的组织特异性microRNA特征
Pub Date : 2014-07-01 DOI: 10.2478/micrnado-2013-0004
R. Farr, Caroline J Taylor, S. Satoor, Michael J. A. Williams, M. Joglekar
Abstract Ever since the discovery of small non-coding RNAs, microRNAs have been identified to play a critical role in development and function of pancreatic insulin-producing beta cells. Research carried out until now demonstrates that microRNAs can specifically target key pancreatic transcription factors and signalling molecules. This in turn may influence changes in insulin production and secretion. microRNAs are also identified in insulin target organs that are altered as a result of hyperglycemia and insulin resistance. Recent studies demonstrate that microRNAs are not only confined to cells but are also detected in biological fluids including serum, plasma and urine. These data indicate that miRNAs may be looked upon having a dual role, as biomarkers and as regulators of disease. We review the existing literature in understanding the role of microRNAs in development, function and death of pancreatic beta cells as well as in the development of metabolic disease. We discuss the possible mechanisms that contribute to identifying the role of microRNAs as sensitive and efficient biomarkers to predict the progression of diabetes. Understanding tissue-specific microRNA signatures and their role as a cause or effect of diabetes would provide more information on progression of this disease.
自从小的非编码rna被发现以来,人们已经发现microrna在胰腺产生胰岛素的β细胞的发育和功能中起着至关重要的作用。迄今为止的研究表明,microrna可以特异性靶向关键的胰腺转录因子和信号分子。这反过来又可能影响胰岛素产生和分泌的变化。在胰岛素靶器官中也发现了由于高血糖和胰岛素抵抗而发生改变的microrna。最近的研究表明,microrna不仅局限于细胞,而且可以在包括血清、血浆和尿液在内的生物液体中检测到。这些数据表明,mirna可能被视为具有双重作用,作为生物标志物和疾病调节剂。我们回顾了现有的文献,以了解microrna在胰腺β细胞的发育、功能和死亡以及代谢性疾病的发展中的作用。我们讨论了可能的机制,有助于确定microrna作为预测糖尿病进展的敏感和有效的生物标志物的作用。了解组织特异性microRNA特征及其作为糖尿病病因或影响的作用将为该疾病的进展提供更多信息。
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引用次数: 3
期刊
Non-coding RNAs in Endocrinology
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