Regular Article
Messenger RNA Profiles in Liver Injury and Stress: A Comparison of Lethal and Nonlethal Rat Models

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Abstract

Liver damage activates processes aimed at repairing damage; simultaneously, liver functions required for survival must be maintained. The expression of genes responsible for both in rat models of lethal (lipopolysaccharide, 90% hepatectomy, and d-galactosamine) and nonlethal (turpentine, 70% hepatectomy, and acetaminophen) liver damage and stress was measured at 3, 6, 12, and 24 h after the intervention and quantitated as the area between the control curves and the test curves (AUC). The expression of genes for cell division and remodeling was upregulated most in the lethal models. The expression of most liver-specific function genes was reduced. Positive AUC was found for ARG, ASL, CPT1, Mdr1b, Mdr2, and PEPCK. It is concluded that a high expression of genes for repair of liver damage is associated with reduced expression of genes for several liver-specific functions, possibly reflecting a limited capacity for transcriptional activity. Maintained or increased expression of selected function genes indicates that the corresponding functions have high priority. The liver sustains metabolic homeostasis ensuring that other organs in the body function normally. Simultaneously, the processes required for the integrity of its own structure and function are maintained as a result of regulated expression of the genes that produce the proteins needed to perform both set of functions.

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    Abbreviations used: ARG, arginase; ASL, argininosuccinate lyase; ASS, argininosuccinate synthetase; AUC, area under curve; Bsep, bile salt exporting pump; C/EBPα, CAAT binding protein alpha; C/EBPβ, CAAT binding protein beta; CPS, carbamoylphosphate synthase-1; CPT1, carnitinepalmiotyl transferase-1; GCS h.c., glutamylcysteine synthetase heavy chain; GCS l.c., glutamylcysteine synthetase light chain; GSTπ, glutathione S-transferase Pi; IGFBP1, insulin growth factor binding protein 1; IGF-I, insulin growth factor-I; IL-6, interleukin-6; IL-6R, interleukin-6 receptor; Mdr1b, multidrug resistance protein 1b; Mdr2, multidrug resistance protein 2; mRNA, messenger ribonucleic acid; Mrp2, multidrug-resembling protein 2; Ntcp, Na-dependent cholate transporting protein; Oatp1, organic ion transport protein 1; Oatp2, organic ion transport protein 2; ODC, ornithine decarboxylase; OTC, ornithine transcarbamylase; PAI-1, plasminogen activator inhibitor 1; PEPCK, phosphoenolpyruvate carbokinase; TNFα, tumor necrosis factor alpha; uPAR, urokinase plasminogen activator receptor; α-AGP, alpha1-acid glycoprotein; α2-M, alpha2-macroglobulin.

    1

    To whom correspondence and reprint requests should be addressed at Laboratory of Hepatology, Rigshospitalet 2151, 9 Blegdamsvej, DK 2100 Copenhagen, Denmark. Fax: +45 3545 2354. E-mail: [email protected].

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