Unknown,Transcriptomics,Genomics,Proteomics

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Effect of splenectomy on liver sinusoidal cells after 70% liver resection in a mouse model

ABSTRACT: In this work, the effect of splenectomy on liver sinusoidal cells was studied. For this purpose in the animals were reproduced splenectomy, and after 7 days 70% liver resection was performed. Animals in which the spleen was intact and only 70% liver resection was performed served as a comparison group. Animals in which only the spleen was removed also served as controls. The animals were removed from the experiment after 24 hours, 3 and 7 days. Liver sinusoidal cells were isolated from the livers of control animals as well as from the liver after 70% resection by magnetic sorting using the CD146 beads. RNA was isolated from the obtained liver sinusoidal cells and used for transcriptome analysis. Liver sinusoidal cells in the regenerating liver were transcriptomically enriched for signaling pathways associated with monocyte migration, cell adhesion and cell death.

INSTRUMENT(S): Affymetrix

ORGANISM(S): Mus musculus

SUBMITTER: Polina Vishnyakova

PROVIDER: E-MTAB-14941 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Following parenchymal loss, the liver regenerates restoring normal mass and metabolic function. Prevailing theories on triggering events leading to regeneration include humoral, metabolic and flow-mediated mechanisms, the latter emphasizing the importance of shear stress mediated nitric oxide (NO) regulation. We aimed to investigate whether the grade of resection and hence the portal venous pressure and sinusoidal shear stress increase, would be reflected in the gene expression profiles in the liver remnant by employing a global porcine cDNA microarray chip with approximately 23 000 genes represented. Six pig livers were resected with 62% (Low Portal Pressure Resection, LPPR) and 75% (High Portal Pressure Resection) resulting in a portal venous pressure increase from a baseline of 6.1 mmHg to 8.2 and 12 mmHg respectively. By sampling consecutive biopsies from the liver remnants we found differentially expressed genes in the HPPR group to have functions related primarily to apoptosis, nitric oxide metabolism and oxidative stress, whereas differentially expressed genes in the LPPR group potentially regulate the cell cycle. Common to both groups was the upregulation of genes regulating inflammation, transport, cell proliferation and development and protein metabolism. Also common to both groups was both up- and downregulation of genes regulating cell-cell signaling, signal transduction, cell adhesion and translation. Genes regulating the metabolism of lipids, hormones, amines, and alcohol were downregulated in both groups. Conclusions: The genetic regenerative response in the liver remnant to varies according to the level of resection. Keywords: time course, treatment comparison Three pigs underwent a 62% liver resection (low-pressure resection, LPR) and three underwent a 75% resection (high-pressure resection, HPR). Biopsies from the liver remnant were taken from all animals at time points 1, 30, 90, minutes and 3, 4 and 6 hours after resection. Expression profiling was conducted by hybridising each sample against a common reference, consisting of liver RNA from an unrelated animal.

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Effect of splenectomy on liver sinusoidal cells after 70% liver resection in a mouse model

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