Creation of a digital slide and tissue microarray resource from a multi-institutional predictive toxicology study in the rat: An initial report from the PredTox group

Mulrane, Laoighse; Rexhepaj, Elton; Smart, Valerie; Callanan, John J.; Orhan, Dıclehan; Eldem, Türkan; Mally, Angela; Schroeder, Susanne; Meyer, Kirstin; Wendt, Maria; O’Shea, Donal F.; Gallagher, William M.

doi:10.1016/j.etp.2007.12.004

Cited by 37 publications

(23 citation statements)

References 20 publications

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“…Average values were calculated as a corrective value. Finally, these values were analyzed using GeneMath, GeneSpring (Silicon Genetics, San Carlos, CA, USA) and other programs (Mulrane et al, 2008).…”

Section: Microarray Detection and Data Analysismentioning

confidence: 99%

Involvement of ERK1/2 signaling in proliferation of eight liver cell types during hepatic regeneration in rats

Chen¹,

Xu²,

Liu³

2013

Genet. Mol. Res.

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ABSTRACT. It has been well established that ERK1/2 signaling, often subdivided into nine types of pathways, can regulate the hepatocyte proliferative response during liver regeneration. However, the effect of ERK1/2 signaling on the proliferation of other hepatic cell types remains unclear. We isolated and purified 8 liver cell types at 10 time points after 2/3 hepatectomy in adult rats. For each cell type, mRNA expression changes for ERK1/2 signaling-involved genes were monitored up to 168 h, using microarrays. Real-time PCR assays were performed for array data verification. The expression levels of these genes varied considerably between different cell types. Integrating microarray results with gene synergical analysis, at the priming phase, activation of integrin/Grb2/Ras pathway in hepatocytes apparently contributed to G0/G1 transition. Two other pathways, G-protein/EPAC/Rap1 and G-protein/PKA/Rap1, were stimulated in hepatic stellate cells, while RTK/PKC/Ras and RTK/Grb2/Ras were stimulated in Kupffer cells. At the progressive phase, the ERK1/2 pathway is involved in hepatocyte replication; three pathways, namely Ca G-protein/EPAC/Rap1, were found to play roles in biliary epithelial cell proliferation, while RTK/PKC/Ras and RTK/Grb2/Ras were involved in Kupffer cell proliferation, and G-protein/PKC/Ras in pit cell proliferation. At the terminal phase, the promotive effect of the ERK1/2 pathway on replication of hepatocytes, biliary epithelial cells, oval cells, hepatic stellate cells, Kupffer cells, and dendritic cells was considerably reduced, possibly due to their differentiation at the end of regeneration. G-protein/PKC/Ras, integrin/Grb2/Ras and G-protein/ PKA/Rap1 pathways were active in sinusoidal endothelial cells, perhaps to aid in their proliferation. We conclude that ERK1/2 has a signaling role in the regulation of proliferation of 8 cell types during liver regeneration process.

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Section: Microarray Detection and Data Analysismentioning

confidence: 99%

Involvement of ERK1/2 signaling in proliferation of eight liver cell types during hepatic regeneration in rats

Chen¹,

Xu²,

Liu³

2013

Genet. Mol. Res.

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“…biomarqueurs et dans le cadre de projets pilotes intégrant des données microscopiques tissulaires et des données protéomiques ou métabolomiques [7]. De telles intégrations de données morphologiques et moléculaires sont par exemple utilisées dans les études à grande échelle en toxicologie pour mieux appréhender les différents résultats de toxicité [8]. L'analyse d'image numé-rique a pu aussi être utilisée pour des études de mécanistique en carcinogenèse.…”

Section: Apport Des Lames Virtuelles à La Recherche Cliniqueunclassified

Les lames virtuelles en recherche expérimentale et en recherche clinique

et al. 2012

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“…Images reflecting gene expression abundance were converted into normalized signal values, and P values, log ratios, and change in P values at each time point were calculated and compared to the normal control group (0 h) using the Affymetrix GCOS 2.0 software. To minimize technical errors from the microarray experiments, isolated HCs from control groups and PH groups were detected using the Rat Genome 230 2.0 Microarray at least 3 times (Amon et al, 2003;Nikitin et al, 2003;Mulrane et al, 2008).…”

Section: Rna Extraction and Rat Genome 230 20 Microarray Detectionmentioning

confidence: 99%

Three branches of phospholipase C signaling pathway promote hepatocyte growth in rat liver regeneration

Xu¹,

Geng²,

Zhou³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. In general, the phospholipase C (PLC) signaling pathway is involved in many physiological activities, including cell growth. However, little is known regarding how the PLC signaling pathway participates in regulating hepatocyte (HC) growth during liver regeneration (LR). To further explore the influence of the PLC signaling pathway on HCs at the cellular level, HCs of high purity and vitality were isolated using Percoll density-gradient centrifugation after partial hepatectomy. The genes of the PLC signaling pathway and target genes of transcription factors in the pathway were obtained by searching the pathways and transcription factor databases, and changes in gene expression of isolated HCs were examined using the Rat Genome 230 2.0 Microarray. The results suggested that various genes involved in the pathway (including 151 known genes and 39 homologous genes) and cell growth (including 262 known genes and 37 homologous genes) were associated with LR. Subsequently, the synergetic effect of these genes in LR was analyzed using a mathematical model (E t ) according to their expression profiles. The results showed that the E t values of G protein- coupled receptor/PLC, integrin/PLC, and growth factor receptor/PLC branches of the PLC pathway were all significantly strengthened during the progression and termination phases of LR. The synergetic effect of target genes, in parallel with target gene-related cell growth, was also enhanced during whole rat LR, suggesting the potential positive effect of PLC on HC growth. The present data indicate that the PLC signaling pathway may promote HC growth through 3 mechanisms during rat LR after partial hepatectomy.

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Creation of a digital slide and tissue microarray resource from a multi-institutional predictive toxicology study in the rat: An initial report from the PredTox group

Cited by 37 publications

References 20 publications

Involvement of ERK1/2 signaling in proliferation of eight liver cell types during hepatic regeneration in rats

Involvement of ERK1/2 signaling in proliferation of eight liver cell types during hepatic regeneration in rats

Les lames virtuelles en recherche expérimentale et en recherche clinique

Three branches of phospholipase C signaling pathway promote hepatocyte growth in rat liver regeneration

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