Rat Life Cycle Kidney miRNA Expression Data
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE64842 | GEO | 2015/01/10
SECONDARY ACCESSION(S): PRJNA272146
REPOSITORIES: GEO
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Project description:Kidney miRNA expression was examined in F344 rats at 2, 5, 6, 8, 15, 21, 78, and 104 weeks of age in both sexes using Agilent miRNA microarrays. 311 miRNAs were found to be expressed in at least one age and sex. Filtering criteria of ?1.5 fold change and ANOVA (FDR <5%) revealed 174 differentially expressed miRNAs in the kidney; 173 and 34 miRNAs exhibiting age and sex effects, respectively. Principal component analysis revealed age effects predominated over sex effects, with 2 week miRNA expression being much different from other ages. No significant sexually dimorphic miRNA expression was observed from 5 to 8 weeks, while the most differential expression (13 miRNAs) was observed at 21 weeks. Potential target genes of these differentially expressed miRNAs were identified. Pathway analysis was used to investigate the possible roles of these target genes in age- and sex-specific differences. Untreated male and female F344 rats from 2, 5, 6, 8, 15, 21, 78, and 104 weeks of age (n=5) were sacrificed by CO2 asphyxiation, whole kidneys collected and homogenized, total RNA, including small RNA fraction, was used for miRNA expression arrays (Agilent).
2015-01-10 | E-GEOD-64842 | biostudies-arrayexpress
Project description:Global miRNA expression was examined in liver tissues from male and female F344 rats over the life span for the purpose of evaluating their possible roles in susceptibility to liver toxicity and disease. Hepatic miRNA expression was characterized at 2, 5, 6, 8, 15, 21, 52, 78, and 104 weeks of age in both sexes using Agilent 8x15k rat miRNA microarrays containing multiple probes for 677 unique miRNAs. Data processing, 75% normalization, and statistical analysis of microarray data were performed in SAS. Functional analysis (Ingenuity) was performed on select miRNAs exhibiting prominent age and sex expression differences. +
2017-02-19 | GSE65169 | GEO
Project description:As the fetal heart develops, cardiomyocyte proliferation potential decreases while fatty acid oxidative capacity increases, a highly regulated transition known as cardiac maturation. Small noncoding RNAs, such as microRNAs (miRNAs), contribute to the establishment and control of tissue-specific transcriptional programs. However, small RNA expression dynamics and genome wide miRNA regulatory networks controlling maturation of the human fetal heart remain poorly understood. Transcriptome profiling of small RNAs revealed the temporal expression patterns of miRNA, piRNA, circRNA, snoRNA, snRNA and tRNA in the developing human heart between 8 and 19 weeks of gestation. Our analysis revealed that miRNAs were the most dynamically expressed small RNA species throughout mid-gestation. Cross-referencing differentially expressed miRNAs and mRNAs predicted 6,200 mRNA targets, 2134 of which were upregulated and 4066 downregulated as gestation progresses. Moreover, we found that downregulated targets of upregulated miRNAs predominantly control cell cycle progression, while upregulated targets of downregulated miRNAs are linked to energy sensing and oxidative metabolism. Furthermore, integration of miRNA and mRNA profiles with proteomes and reporter metabolites revealed that proteins encoded in mRNA targets, and their associated metabolites, mediate fatty acid oxidation and are enriched as the heart develops.This study revealed the small RNAome of the maturing human fetal heart. Furthermore, our findings suggest that coordinated activation and repression of miRNA expression throughout mid-gestation is essential to establish a dynamic miRNA-mRNA-protein network that decreases cardiomyocyte proliferation potential while increasing the oxidative capacity of the maturing human fetal heart.
2024-01-26 | PXD044936 | Pride
Project description:Clear cell renal cell carcinomas (ccRCC) are characterized by arm-wide chromosomal alterations. Loss at 14q is associated with disease aggressiveness in ccRCC, which responds poorly to chemotherapeutics. The 14q locus contains one of the largest miRNA clusters in the human genome; however, little is known about the contribution of these miRNAs to ccRCC pathogenesis. In this regard, we investigated the expression pattern of selected miRNAs at the 14q32 locus in TCGA kidney tumors and in ccRCC cell lines. We validated that the miRNA cluster is downregulated in ccRCC (and cell lines) as well as in papillary kidney tumors relative to normal kidney tissues and primary renal proximal tubule epithelial (RPTEC) cells. We demonstrated that agents modulating expression of DNMT1 (e.g., 5-Aza-deoxycytidine) could modulate miRNA expression in ccRCC cell lines. Lysophosphatidic acid (LPA, a Lysophospholipid mediator elevated in ccRCC) not only increased labile iron content but also modulated expression of 14q32 miRNAs. Through an overexpression approach targeting a subset of 14q32 miRNAs (specifically at subcluster A: miR-431, miR-432, miR-127, and miR-433) in 769-P cells, we uncovered changes in cellular viability and claudin-1, a tight junction marker. A global proteomic approach was implemented using these miRNA overexpressing cell lines which uncovered ATXN2 as a highly downregulated target, which has a role in chronic kidney disease pathogenesis. Collectively, these findings support a contribution of miRNAs at 14q32 in ccRCC pathogenesis.
2023-05-10 | PXD036428 | Pride
Project description:The kidney functions in key physiological processes to filter blood and regulate blood pressure via key molecular transporters and ion channels. Sex-specific differences have been observed in renal disease incidence and progression as well as acute kidney injury in response to certain drugs. Although advances have been made in characterizing the molecular components involved in various kidney functions, the molecular mechanisms responsible for sex differences are not well understood. We hypothesized that the basal expression levels of genes involved in various kidney functions throughout the life cycle will influence sex-specific susceptibilities to adverse renal events. Untreated female F344 rats from 2, 5, 6, 8, 15, 21, 78, and 104 weeks of age (n=5) were sacrificed by CO2 asphyxiation, whole kidneys collected and homogenized, total RNA used for whole genome expression arrays (Agilent).
2013-07-31 | E-GEOD-47069 | biostudies-arrayexpress
Project description:Age- and sex-related susceptibility to adverse drug reactions is a key concern in understanding drug safety and disease progression. We hypothesize that the underlying suite of hepatic genes expressed at various developmental and life-cycle stages will impact susceptibility to adverse drug reactions. Thus, understanding the basal expression patterns of genes throughout the life span of the rat model species in both sexes will inform our assessments of adverse drug reactions. The liver plays a central role in the metabolism and biotransformation of drugs via key cellular pathways. Untreated, male and female F344 rats were sacrificed at 2, 5, 6, 8, 15, 21, 52, 78, and 104 weeks of age. Liver tissues were collected for histology and gene expression analysis. Whole-genome rat microarrays (44,000 features) were used to query global expression profiles. An initial list of active genes was selected using a 2-way ANOVA with a p-value cutoff of 0.05 and 1.5 fold-change difference from mean expression. Three dimensional principal component analyses revealed notable expression profile divergence between males and females after 5 weeks with greatest differences observed at 21 and 52 weeks before converging again at 104 weeks. Furthermore, k-means clustering identified groups of genes that displayed specific developmental and age-related patterns of expression. Various adult aging-related clusters included genes involved in pathways related to susceptibility to adverse drug effects such as xenobiotic metabolism, DNA damage repair, and oxidative stress. These results suggest an underlying role for genes in these specific clusters in potentiating age- and sex-related susceptibilities to adverse health effects.
2010-06-24 | GSE21335 | GEO
Project description:Poor maternal nutrition causes intrauterine growth restriction (IUGR); however, its effects on fetal cardiac development are unclear. We have developed a baboon model of moderate maternal undernutrition, leading to IUGR. We hypothesized that the IUGR affects fetal cardiac structure and metabolism. Six control pregnant baboons ate ad-libitum (CTRL)) or 70% CTRL from 0.16 of gestation (G). Fetuses were euthanized at C-section at 0.9G under general anesthesia. Male but not female IUGR fetuses showed left ventricular fibrosis inversely correlated with birth weight. Expression of extracellular matrix protein TSP-1 was increased (p<0.05) in male IUGR. Expression of cardiac fibrotic markers TGFß, SMAD3 and ALK-1 were downregulated in male IUGRs with no difference in females. Autophagy was present in male IUGR evidenced by upregulation of ATG7 expression and lipidation LC3B. Global miRNA expression profiling revealed 56 annotated and novel cardiac miRNAs exclusively dysregulated in female IUGR, and 38 cardiac miRNAs were exclusively dysregulated in males (p<0.05). Fifteen (CTRL) and 23 (IUGR) miRNAs, were differentially expressed between males and females (p<0.05) suggesting sexual dimorphism, which can be at least partially explained by differential expression of upstream transcription factors (e.g. HNF4a, and NF?B p50). Lipidomics analysis of fetal cardiac tissue exhibited a net increase in diacylglycerol and plasmalogens and a decrease in triglycerides and phosphatidylcholines. In summary, IUGR resulting from decreased maternal nutrition is associated with sex-dependent dysregulations in cardiac structure, miRNA expression, and lipid metabolism. If these changes persist postnatally, they may program offspring for higher later life cardiac risk.
2018-04-30 | MTBLS426 | MetaboLights
Project description:The kidney is important for a number of physiological processes including blood filtering, blood pressure regulation and proper excretion of many drugs and xenobiotics. Age is a predisposing condition for susceptibility to chronic kidney disease and progression as well as acute kidney injury that may arise due to the adverse effects of some drugs. Age-related differences in kidney biology, therefore, are a key concern in understanding drug safety and disease progression. We hypothesize that the underlying suite of genes expressed in the kidney at various life cycle stages will impact susceptibility to adverse drug reactions. Therefore, establishing changes in baseline expression data between these life stages is the first and necessary step in evaluating this hypothesis. Untreated male F344 rats from 2, 5, 6, 8, 15, 21, 78, and 104 weeks of age (n=5) were sacrificed by CO2 asphyxiation, whole kidneys collected and homogenized, total RNA used for whole genome expression arrays (Agilent).
2013-07-31 | E-GEOD-47068 | biostudies-arrayexpress
Project description:Aristolochic acid (AA) is an active component of herbal drugs derived from the Aristolochia species that have been used for medicinal purposes since antiquity. However, AA is genotoxic and induces tumors in animals and humans. AA induces mutations and tumors in the kidney but solely mutations in the liver. To evaluate whether miRNAs could indicate AA’s tissue-specific carcinogenicity and mutagenicity, we first conducted microarray analysis of miRNA expression in kidneys and livers of rats treated with a carcinogenic dose of AA. Then, miR-21, a biomarker for carcinogenicity, and miR-34a, a biomarker for mutagenicity, the two miRNAs whose expressions were most altered, were evaluated for their expression in the kidney (the AA’s mutagenic and carcinogenic target tissue), liver (the AA’s mutagenic target tissue), and testis, the non-target tissue where neither tumors nor mutation induction was found in previous studies and in this study. Genomic analysis of miRNA expression for kidney and liver samples showed that miRNA expression was globally changed by the treatment. Nineteen miRNAs were significantly dysregulated by the treatment in the kidney. Most of these miRNAs are related to carcinogenesis. Only one miRNA, miR-34a, was differentially expressed in the liver. Expression of miR-21 was induced in the kidney by AA treatment in a dose-dependent manner while no changes occurred in the liver or testis, indicating that the kidney is the carcinogenic target. miR-34a was dose-dependently up-regulated in the kidneys and livers of rats treated with AA, but not in the testis, suggesting that the kidney and liver are mutagenic target tissues, but the testis is not. Our results demonstrate that miRNA profiles can reflect the AA’s carcinogenicity in a tissue-specific manner while specific miRNAs can signify the target tissues for carcinogenicity or mutagenicity of AA.
2013-11-10 | GSE50946 | GEO
Project description:MicroRNAs (miRNAs) present in tissues and biofluids are emerging as sensitive and specific safety biomarkers. MiRNAs have not been thoroughly described in M. fascicularis, an animal model used in pharmaceutical industry especially in drug safety evaluation. Here we investigated the miRNAs in M. fascicularis. For Macaca mulatta, a closely related species of M.fascicularis, 619 stem-loop precursor miRNAs (pre-miRNAs) and 914 mature miRNAs are available in miRBase version 21. Using M. mulatta miRNAs as a reference list and homology search tools, we identified 604 pre-miRNAs and 913 mature miRNAs in the genome of M.fascicularis. In order to validate the miRNAs identified by homology search we attempted to sequence miRNAs expressed in kidney cortex from M. fascicularis. MiRNAs expressed in kidney cortex may indeed be released in urine upon kidney cortex damage and be potentially used to monitor drug induced kidney injury. Hence small RNA sequencing libraries were prepared using kidney cortex tissues obtained from three naive M. fascicularis and sequenced. Analysis of sequencing data indicated that 432 out of 913 mature miRNAs were expressed in kidney cortex tissues. Assigning these 432 miRNAs to pre-miRNAs revealed that 273 were expressed from both the -5p and -3p arms of 150 pre-miRNAs and 159 miRNAs expressed from either the -5p or -3p arm of 176 pre-miRNAs. Mapping sequencing reads to pre-miRNAs also facilitated the detection of twenty-two new miRNAs. To substantiate miRNAs identified by small RNA sequencing, 313 miRNAs were examined by RT-qPCR. Expression of 262 miRNAs in kidney cortex tissues ware confirmed by TaqMan microRNA RT-qPCR assays. Analysis of kidney cortex miRNA targeted genes suggested that they play important role in kidney development and function. Data presented in this study may serve as a valuable resource to assess the renal safety biomarker potential of miRNAs in Cynomolgus monkeys.
2016-09-13 | GSE86836 | GEO