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Alteration of mRNA and microRNA expression profiles in rat muscular type vasculature in early postnatal development.

ABSTRACT: The vascular system is characterized by a high degree of plasticity. In particular, functional and structural remodeling of the arterial system takes place during early postnatal development. However, the mechanisms providing such alterations in the rapidly growing organisms are poorly understood, especially for the peripheral vasculature. To explore this, we performed mRNA- and miRNA microarray analysis on muscular type saphenous arteries of young (10-12 days) and adult (2-3 months) rats. Thirty-eight significant pathways (such as oxidative phosphorylation, MAPK signaling, metabolism, cell cycle, DNA replication and focal adhesion) were obtained on differentially regulated genes during postnatal development. Many differentially regulated genes were determined as target- and miRNA-hubs. We also found 92 miRNAs differentially expressed in arteries of young and adult rats. Several significantly regulated pathways were found on these regulated miRNAs. Interestingly, these biological cascades also contain those significantly enriched pathways that were previously identified based on the differently expressed genes. Our data indicate that the expression of many genes involved in the regulation of pathways that are relevant for different functions in arteries may be under the control of miRNAs and these miRNAs regulate the functional, and structural remodeling occurring in the vascular system during early postnatal development.

SUBMITTER: Gaynullina D

PROVIDER: S-EPMC4466593 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Alteration of mRNA and microRNA expression profiles in rat muscular type vasculature in early postnatal development.

Gaynullina Dina D Dweep Harsh H Gloe Torsten T Tarasova Olga S OS Sticht Carsten C Gretz Norbert N Schubert Rudolf R

Scientific reports 20150615

The vascular system is characterized by a high degree of plasticity. In particular, functional and structural remodeling of the arterial system takes place during early postnatal development. However, the mechanisms providing such alterations in the rapidly growing organisms are poorly understood, especially for the peripheral vasculature. To explore this, we performed mRNA- and miRNA microarray analysis on muscular type saphenous arteries of young (10-12 days) and adult (2-3 months) rats. Thirt ...[more]

PMID: 26073182

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Project description:PurposeExposure to radiation provokes cellular responses, which are likely regulated by gene expression networks. MicroRNAs are small non-coding RNAs, which regulate gene expression by promoting mRNA degradation or inhibiting protein translation. The expression patterns of both mRNA and miRNA during the radiation-induced lung injury (RILI) remain less characterized and the role of miRNAs in the regulation of this process has not been studied. The present study sought to evaluate miRNA and mRNA expression profiles in the rat lung after irradiation.Methods and materialsMale Wistar rats were subjected to single dose irradiation with 20 Gy using 6 MV x-rays to the right lung. (A dose rate of 5 Gy/min was applied). Rats were sacrificed at 3, 12 and 26 weeks after irradiation, and morphological changes in the lung were examined by haematoxylin and eosin. The miRNA and mRNA expression profiles were evaluated by microarrays and followed by quantitative RT-PCR analysis.ResultsA cDNA microarray analysis found 2183 transcripts being up-regulated and 2917 transcripts down-regulated (P???0.05, ?2.0 fold change) in the lung tissues after irradiation. Likewise, a miRNAs microarray analysis indicated 15 miRNA species being up-regulated and 8 down-regulated (P???0.05). Subsequent bioinformatics analyses of the differentially expressed mRNA and miRNAs revealed that alterations in mRNA expression following irradiation were negatively correlated with miRNAs expression.ConclusionsOur results provide evidence indicating that irradiation induces alterations of mRNA and miRNA expression in rat lung and that there is a negative correlation of mRNA and miRNA expression levels after irradiation. These findings significantly advance our understanding of the regulatory mechanisms underlying the pathophysiology of radiation-induced lung injury. In summary, RILI does not develop gradually in a linear process. In fact, different cell types interact via cytokines in a very complex network. Furthermore, this study suggests that microRNAs may serve an important role in the pathogenesis of RILI and that understanding their role in RILI may have a significant effect on patient management and diagnosis in the future.

Project description:MicroRNAs (miRNAs) are small non-coding RNAs that play critical roles in diverse biological processes via regulation of gene expression including in skeletal muscles. In the current study, miRNA expression profile was investigated in longissimus muscle biopsies of malignant hyperthermia syndrome-negative Duroc and Pietrain pigs with distinct muscle metabolic properties in order to explore the regulatory role of miRNAs related to mitochondrial respiratory activity and metabolic enzyme activity in skeletal muscle.A comparative analysis of the miRNA expression profile between Duroc and Pietrain pigs was performed, followed by integration with mRNA profiles based on their pairwise correlation and computational target prediction. The identified target genes were enriched in protein ubiquitination pathway, stem cell pluripotency and geranylgeranyl diphosphate biosynthesis, as well as skeletal and muscular system development. Next, we analyzed the correlation between individual miRNAs and phenotypical traits including muscle fiber type, mitochondrial respiratory activity, metabolic enzyme activity and adenosine phosphate concentrations, and constructed the regulatory miRNA-mRNA networks associated with energy metabolism. It is noteworthy that miR-25 targeting BMPR2 and IRS1, miR-363 targeting USP24, miR-28 targeting HECW2 and miR-210 targeting ATP5I, ME3, MTCH1 and CPT2 were highly associated with slow-twitch oxidative fibers, fast-twitch oxidative fibers, ADP and ATP concentration suggesting an essential role of the miRNA-mRNA regulatory networking in modulating the mitochondrial energy expenditure in the porcine muscle. In the identified miRNA-mRNA network, a tight relationship between mitochondrial and ubiquitin proteasome system at the level of gene expression was observed. It revealed a link between these two systems contributing to energy metabolism of skeletal muscle under physiological conditions.We assembled miRNA-mRNA regulatory networks based on divergent muscle properties between different pig breeds and further with the correlation analysis of expressed genes and phenotypic measurements. These complex networks relate to muscle fiber type, metabolic enzyme activity and ATP production and may contribute to divergent muscle phenotypes by fine-tuning the expression of genes. Altogether, the results provide an insight into a regulatory role of miRNAs in muscular energy metabolisms and may have an implication on meat quality and production.

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Alteration of mRNA and microRNA expression profiles in rat muscular type vasculature in early postnatal development.

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Alteration of mRNA and microRNA expression profiles in rat muscular type vasculature in early postnatal development.

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