Regenerative response in the pig liver remnant varies with the degree of resection and rise in portal pressure

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  • Kim Erlend Mortensen, Department of Digestive Surgery, University Hospital of Northern-Norway, Norge
  • Lene Nagsrrup Conley
  • Jakob Hedegaard
  • Trine Kalstad, Laboratory of Surgical Research, Institute of Clinical Medicine, University of Tromsø, Norge
  • Peter Sorensen
  • Christian Bendixen
  • Arthur Revhaug, Laboratory of Surgical Research, Institute of Clinical Medicine, University of Tromsø, Norge
  • Biostatistik
  • Institut for Genetik og Bioteknologi
  • Molekylær Genetik og Systembiologi
After 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 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 using a global porcine cDNA microarray chip with ~23,000 genes represented. Six pig livers were resected with 62% (low portal pressure resection) and 75% (high portal pressure resection), resulting in a portal venous pressure increase from a baseline of 6.1-8.2 and 12 mmHg, respectively. By sampling consecutive biopsies from the liver remnants, we found differentially expressed genes in the high portal pressure resection group to have functions related primarily to apoptosis, nitric oxide metabolism and oxidative stress, whereas differentially expressed genes in the low portal pressure resection group potentially regulate the cell cycle. Common to both groups was the upregulation of genes regulating inflammation, transport, cell proliferation, 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. In conclusion, the genetic regenerative response in the liver remnant to varies according to the level of resection
Udgivelsesdato: March
OriginalsprogEngelsk
TidsskriftAmerican Journal of Physiology: Gastrointestinal and Liver Physiology
Vol/bind294
Nummer3
Sider (fra-til)G818-G830
ISSN0193-1857
DOI
StatusUdgivet - 2008

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