Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

MicroRNA array analysis during the regenerative peak following rat liver resection

ABSTRACT: The liver has the unique capacity to regenerate after surgical resection. However, the regulation of liver regeneration is not completely understood. We performed miRNA microarray analyses of liver tissue from Wistar rats at different time points after 70% partial hepatectomy (0, 2, 6, 12, 24, 48 hours, and 5 days) and after sham laparotomy (12, 24, and 48 hours). We demonstrate that miRNA expression patterns changed during liver regeneration and that these changes were most evident during the peak of DNA replication at 24 hours after resection. Expression of 13 miRNAs, including five members of the let-7 family, was significantly reduced 12-48 hours after resection, whereas 3 miRNAs were significantly upregulated (> 25% change). We provide a temporal miRNA expression dataset of the regenerating rat liver, which indicates a primary function for miRNA during the peak of DNA replication. These data will assist further functional studies on the role of miRNAs during liver regeneration. This project analyzed the miRNA expression in 30 different sample types of the organism rattus norvegicus. The miRNA expression was compared at 7 different growth time points after liver resection (0, 2, 6, 12, 24, 48 hours, 5 days) and at 3 different time points after sham laparotomy (12, 24, and 48 hours). Three biological replicates were used per time point.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Nathanael Raschzok

PROVIDER: E-GEOD-23696 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Temporal expression profiles indicate a primary function for microRNA during the peak of DNA replication after rat partial hepatectomy.

Raschzok Nathanael N Werner Wiebke W Sallmon Hannes H Billecke Nils N Dame Christof C Neuhaus Peter P Sauer Igor M IM

American journal of physiology. Regulatory, integrative and comparative physiology 20110323 6

The liver has the unique capacity to regenerate after surgical resection. However, the regulation of liver regeneration is not completely understood. Recent reports indicate an essential role for small noncoding microRNAs (miRNAs) in the regulation of hepatic development, carcinogenesis, and early regeneration. We hypothesized that miRNAs are critically involved in all phases of liver regeneration after partial hepatectomy. We performed miRNA microarray analyses after 70% partial hepatectomy in ...[more]

PMID: 21430077

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Project description:MicroRNAs (miRNAs) repress the expression levels of genes by binding to mRNA transcripts, acting as master regulators of cellular processes. Differential expression of miRNAs has been linked to viral-associated diseases involving members of the hepacivirus, herpesvirus, and retrovirus families. In contrast, limited biological and molecular information has been reported on the potential role of cellular miRNAs in the lifecycle of influenza A viruses (infA). In this study, we hypothesize that elucidating the miRNA expression signatures induced by low-pathogenic swine-origin influenza A virus (S-OIV) pandemic H1N1 (2009) and highly pathogenic avian-origin (A-OIV) H7N7 (2003) infections could reveal temporal and strain-specific miRNA fingerprints during the viral lifecycle, shedding important insights into the potential role of cellular miRNAs in host-infA interactions. Using a microfluidic microarray platform, we profiled cellular miRNA expression in human A549 cells infected with S- and A-OIVs at multiple time-points during the viral lifecycle, including global gene expression profiling during S-OIV infection. Using target prediction and pathway enrichment analyses, we identified the key cellular pathways associated with the differentially expressed miRNAs and predicted mRNA targets during infA infection, including immune system, cell proliferation, apoptosis, cell cycle, and DNA replication and repair. By identifying the specific and dynamic molecular phenotypic changes (microRNAome) triggered by S- and A-OIV infection in human cells, we provide experimental evidence demonstrating a series of temporal- and strain-specific host molecular responses involving different combinatorial contributions of multiple cellular miRNAs. Our results also identify novel potential exosomal miRNA biomarkers associated with pandemic S-OIV and deadly A-OIV-host infection. Control (mock-infected) samples: 12, Infected samples: 6, for each time-point (0, 4, 8, 24, 48 and 72 hours post infection). Seven replicates for each miRNA were found on the microarray chips, for which the median has been retained. The experiment was performed in six replicates.

Project description:The liverM-bM-^@M-^Ys remarkable capacity to regenerate allows it to carry out vital life-supporting functions despite unrelenting pathogen and toxin-induced injury. Unchecked, this capability also leads to cirrhosis, a burgeoning global disease burden. Existing animal models only partially recapitulate human liver regeneration, which hitherto has not been systematically studied. We investigated human liver regeneration in a unique model of liver transplantation. Here we show coordinated changes in expression of microRNA (miRNA) during regeneration that drive proliferation, innate immunity and angiogenesis. Failed regeneration is associated with distinct miRNAs enforcing cell cycle inhibition and DNA methylation. The miRNA expression associated with successful or failed regeneration when recapitulated in vitro, triggered expression of cardinal regeneration-linked genes promoting cell cycle entry or inhibition, respectively. Furthermore, inhibition of three miRNAs whose downregulation is associated with successful regeneration, induced proliferation in vitro. Our data indicate that human liver regeneration is orchestrated by distinct miRNAs determining cell cycle fate. Their manipulation may obviate the need for transplantation by enforcing successful regeneration in the liver and other solid organs. We compared a group of seven patients with successful regeneration (RG) after auxiliary liver transplant (ALT) to four patients who also had ALT but failed to regenerate (NRG). Regeneration was quantified by volume expansion using radiographic imaging; functional recovery was assessed using nuclear isotope scanning and hepatocellular regeneration using histology. Based on histological assessment, three time points were selected for both groups (RG and NRG). Biopsies were taken at the time of transplant and at different intervals post-transplant. Since sample acquisition was driven by clinical necessity, widely discrepant time intervals existed between T=1, T=2 and T=3 for the patients. RNA was extracted from archived histology samples of the RG and NRG, and miRNA expression was analysed using the Affymetrix GeneChip miRNA 1.0 assays. This submission does not include NRG samples taken at time point 3.

Dataset Information

MicroRNA array analysis during the regenerative peak following rat liver resection

Publications

Temporal expression profiles indicate a primary function for microRNA during the peak of DNA replication after rat partial hepatectomy.

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