Gene expression profile in the regenerating rat liver after partial hepatectomy

Fukuhara, Yasuyuki; Hirasawa, Akira; Li, Xiao Kang; Kawasaki, Mikiko; Fujino, Masayuki; Funeshima, Naoko; Katsuma, Susumu; Shiojima, Satoshi; Yamada, Masahiro; Okuyama, Torayuki; Suzuki, Seiichi; Tsujimoto, Gozoh

doi:10.1016/s0168-8278(03)00077-1

Cited by 89 publications

(71 citation statements)

References 26 publications

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“…The acceleration of growth of hypertrophic liver lobes after application of IL-6 confirmed results gained at in vitro models and in experiments in small laboratory animals (Cornell,1990, Fukuhara, 2003. The selected concentration of applied cytokine initiated acceleration of regeneration of liver parenchyma in non-occluded liver lobes (Baier,2006, Heinrich, 2006.…”

Section: Functional Liver Remnant Volumesupporting

confidence: 58%

“…The proliferation of primed hepatocytes is regulated positively by Hepatocyte growth factor (HGF), Epidermal growth factor (EGF), Insulin-like growth factor (IGF), Transforming growth factor-alpha (TGF-), etc. The termination of proliferation and stimulation of hepatocyte to differentiation, final remodelation of liver tissue and production of extracellular matrix is controled by Transforming growth factor-beta (TGF-) (Fukuhara, 2003, Mangnall, 2003, Zimmermann, 2004. TGF-1 plays the most important role in starting the remodelling of the extracellular matrix and restoration of the original structure of the liver parenchyma.…”

Section: Introductionmentioning

confidence: 99%

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Liver Parenchyma Regeneration in Connection with Extended Surgical Procedure - Experiment on Large Animal

Liška¹,

Třeška²,

Mírka³

et al. 2012

Liver Regeneration

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Section: Functional Liver Remnant Volumesupporting

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Liver Parenchyma Regeneration in Connection with Extended Surgical Procedure - Experiment on Large Animal

Liška¹,

Třeška²,

Mírka³

et al. 2012

Liver Regeneration

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“…In terms of hemostasis, the production and secretion of the coagulation factors, anti-coagulant factors, and fibrinolytic factors are highly dependent on the hepatocytes in the liver [9][10][11][12] . There is evidence that some of the liver-specific proteins have temporal suppression in their production during compensatory liver regeneration [5,13,14] . Although the kinetics for the coagulation and/or fibrinolytic factors during compensatory liver regeneration have been investigated in the past [15,16] , comprehensive analyses assessing the gene expression profiles of the coagulation factors and their related proteins in combination with their plasma activities during DH-mediated liver regeneration have not yet been documented.…”

Section: Introductionmentioning

confidence: 99%

Effects on coagulation factor production following primaryhepatomitogen-induced direct hyperplasia

Tatsumi

Ohashi²,

Taminishi³

et al. 2009

WJG

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AIM:To investigate the molecular mechanisms involved in coagulation factor expression and/or function during direct hyperplasia (DH)-mediated liver regeneration. METHODS:Direct hyperplasia-mediated liver regeneration was induced in female C57BL/6 mice by administering 1,4-bis[2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP), a representative hepatomitogen. Mice were weighed and sacrificed at various time points [Day 0 (D0: prior to injection), 3 h, D1, D2, D3, and D10] after TCPOBOP administration to obtain liver and blood samples. Using the RNA samples extracted from the liver, a comprehensive analysis was performed on the hepatic gene expression profiling of coagulation-related factors by real-time RT-PCR (fibrinogen, prothrombin, factors Ⅴ, Ⅶ, Ⅷ, Ⅸ, Ⅹ, Ⅺ, Ⅻ, XⅢβ, plasminogen, antithrombin, protein C, protein S, ADAMTS13, and VWF). The corresponding plasma levels of coagulation factors (fibrinogen, prothrombin, factors Ⅴ, Ⅶ, Ⅷ, Ⅸ, Ⅹ, Ⅺ, Ⅻ, XⅢ, and VWF) were also analyzed and compared with their mRNA levels. RESULTS:Gavage administration of TCPOBOP (3 mg/kg body weight) resulted in a marked and gradual increase in the weight of the mouse livers relative to the total body weight to 220% by D10 relative to the D0 (control) ratios. At the peak of liver regeneration (D1 and D2), the gene expression levels for most of the coagulationrelated factors (fibrinogen, prothrombin, factors Ⅴ, Ⅶ, Ⅷ, Ⅸ, Ⅺ, Ⅻ, XⅢβ, plasminogen, antithrombin, protein C, ADAMTS13, VWF) were found to be downregulated in a time-dependent manner, and gradually recovered by D10 to the basal levels. Only mRNA levels of factor Ⅹ and protein S failed to show any decrease during the regenerative phase. As for the plasma levels, 5 clotting factors (prothrombin, factors Ⅷ, Ⅸ, Ⅺ, and Ⅻ) demonstrated a significant decrease (P < 0.05) during the regeneration phase compared with D0. Among these 5 factors, factor Ⅸ and factor Ⅺ showed the most dramatic decline in their activities by about 50% at D2 compared to the basal levels, and these reductions in plasma activity for both factors were consistent with our RT-PCR findings. In contrast, the plasma activities of the other coagulation factors (fibrinogen, factors Ⅴ, Ⅶ, XⅢ, and VWF) were not significantly reduced, despite the reduction in the liver mRNA levels. Unlike the other factors, FX showed a temporal increase in its plasma activity, with significant increases (P < 0.05) detected at D1. CONCLUSION:Investigating the coagulation cascade protein profiles during liver regeneration by DH may help to better understand the basic biology of the liver under normal and pathological conditions.

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“…During the first 4 h after hepatectomy in the mouse, only 11 transcription factors were up-regulated during regeneration among 6500 genes examined (13). In the rat, regeneration was associated with induction of only one transcription factor, hepatocyte nuclear factor 4 (14). Another extensive microarray analysis examining networks active during liver regeneration revealed a dramatic shift toward genes involved in cytoskeleton assembly and DNA synthesis; in contrast, no shift toward genes involving transcription was identified (15).…”

mentioning

confidence: 99%

Restoration of Liver Mass after Injury Requires Proliferative and Not Embryonic Transcriptional Patterns

Otu

Naxerova

et al. 2007

Journal of Biological Chemistry

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Normal adult liver is uniquely capable of renewal and repair after injury. Whether this response represents simple hyperplasia of various liver elements or requires recapitulation of the genetic program of the developing liver is not known. To study these possibilities, we examined transcriptional programs of adult liver after partial hepatectomy and contrasted these with developing embryonic liver. Principal component analysis demonstrated that the time series of gene expression during liver regeneration does not segregate according to developmental transcription patterns. Gene ontology analysis revealed that liver restoration after hepatectomy and liver development differ dramatically with regard to transcription factors and chromatin structure modification. In contrast, the tissues are similar with regard to proliferation-associated genes. Consistent with these findings, real-time polymerase chain reaction showed transcription factors known to be important in liver development are not induced during liver regeneration. These three lines of evidence suggest that at a transcriptional level restoration of liver mass after injury is best described as hepatocyte hyperplasia and not true regeneration. We speculate this novel pattern of gene expression may underlie the unique capacity of the liver to repair itself after injury.

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Gene expression profile in the regenerating rat liver after partial hepatectomy

Cited by 89 publications

References 26 publications

Liver Parenchyma Regeneration in Connection with Extended Surgical Procedure - Experiment on Large Animal

Liver Parenchyma Regeneration in Connection with Extended Surgical Procedure - Experiment on Large Animal

Effects on coagulation factor production following primaryhepatomitogen-induced direct hyperplasia

Restoration of Liver Mass after Injury Requires Proliferative and Not Embryonic Transcriptional Patterns

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