Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “LIVER REGENERATION”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 397 records · Page 22Linked to original sources
PubMed1994

Rapid induction of mRNAs for liver regeneration factor and insulin-like growth factor binding protein-1 in primary cultures of rat hepatocytes by hepatocyte growth factor and epidermal growth factor.

Liver regeneration factor belongs to the leucine-zipper family of transcription factors. It was originally cloned and characterized through differential screening of a regenerating rat liver cDNA library. The mRNA for liver regeneration factor-1 is barely detectable in normal rat liver but is dramatically induced after two-thirds hepatectomy, with a peak 1 to 3 hr after surgery. The nature of the signaling molecule(s) for this rapid induction is not known. It has been suggested that the liver regeneration factor-1 protein product, through complex interactions with other transcription factors such as c-Jun and Jun-B, controls expression of genes that are required during the G1 phase of hepatic growth. Hepatocyte growth factor has been shown to be the most potent mitogen for hepatocytes in vitro and in vivo. Plasma levels of hepatocyte growth factor rapidly (within 30 min) increase after loss of hepatic parenchyma induced by partial hepatectomy or carbon tetrachloride treatment. It has been postulated that hepatocyte growth factor plays a crucial role in stimulating the hepatocyte to enter the cell cycle. In this communication, we report that addition of pure hepatocyte growth factor to primary cultures of rat hepatocytes in the absence of serum and insulin results in rapid and transient induction of liver regeneration factor-1 mRNA (more than 20-fold) with a peak of expression 1 hr after treatment. The levels of jun-B and c-fos mRNAs, which are also known to be induced during the early hours of liver regeneration, were also increased after treatment of isolated hepatocytes with hepatocyte growth factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Activating Transcription Factor 3↗
PubMed2003

Retrorsine: a kinetic study of its influence on rat liver regeneration in the portal branch ligation model.

BACKGROUND: Retrorsine, a naturally occurring pyrrolizidine alkaloid, impairs liver regeneration after partial hepatectomy by mechanisms that are still unclear. AIM: The aim of the study was to clarify the influence of retrorsine on cell cycle progression in the regenerating liver lobes of rats after portal branch ligation (PBL). METHODS: Liver weight, protein and DNA contents, DNA synthesis (5'-bromodeoxyuridine (BrdU) incorporation) and cellular levels of Cyclin E, CDK-2, CDK-4 and proliferating cell nuclear antigen (PCNA) were assessed before and 24, 48, 72 and 168 h after PBL. RESULTS: Before surgery, higher levels of cyclin E, CDK-2, CDK-4 and PCNA as well as BrdU incorporation were found in the liver of retrorsine-treated rats than in untreated rats. Liver weight gain, protein and DNA synthesis as well as induction of cell cycle related proteins were all strongly impaired by retrorsine in the regenerating lobes after PBL. CONCLUSIONS: In conclusion, retrorsine impairs liver regeneration in the PBL model not only by an S or G2/M phase block, but also by a block located before the G1/S transition of the cell cycle.

Animals↗
PubMed1985

Alterations in fucosyl oligosaccharides of glycoproteins during rat liver regeneration.

[3H]Fucose-labelled glycopeptides in the slices of liver 24h after partial hepatectomy were fractionated on Sephadex G-50. Glycopeptides from regenerating liver contained a higher proportion of lower-Mr components than did controls. Regenerating liver contained a higher proportion of glycopeptides that were bound to concanavalin A-Sepharose and were subsequently eluted with 20mM-methyl alpha-D-glucopyranoside than did controls. Concanavalin A-bound glycopeptides from each source were entirely bound to a lentil lectin-Sepharose column. Both the concanavalin A-bound and -unbound fractions from regenerating liver were indistinguishable from the respective controls by Bio-Gel P6 column chromatography and neuraminidase digestion. These results show that fucosyl glycopeptides from regenerating liver contain a higher proportion of biantennary species with core fucose residues than do controls. Glycopeptides from regenerating livers 12h, 72h and 144h after partial hepatectomy were also examined; however, the difference was not significant. These observations suggest that the alterations in fucosyl glycopeptides may be related to rapid growth of hepatocytes 24h after partial hepatectomy. No significant difference was found in either [3H]mannose- or [3H]fucose-labelled glycoproteins from regenerating liver and from controls by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, suggesting that the alteration in glycopeptides should depend on some differences in the late stage of oligosaccharide processing.

Animals↗
PubMed1996

Identification of homeobox genes expressed during the process of rat liver regeneration after partial hepatectomy.

Homeobox (HBox) genes are well-known to be involved in development and differentiation. To ascertain a role of HBox genes in the process of liver regeneration, we identified HBox genes expressed at various times after partial hepatectomy in rats (at 0 hr, 1 hr, 2 days, and 4 days) by using reverse transcription-polymerase chain reaction (RT-PCR), cloning, and sequencing techniques. By the competitive RT-PCR method using generic primers, expression levels of HBox genes in regenerating livers were estimated at as low as only 0.4-2% of that in 14-day embryonic liver; however, we identified multiple HBox genes at different stages. Comparing sets of HBox genes identified at different stages, we could find two candidates of stage specifically expressed HBox genes (one rat caudal-related gene, RCdx-3, stimulated at 1 hr, and one rat Hox gene, RHoxB5, repressed after hepatectomy) and continuous expression of five Hox genes (RHoxA1, A4, A5, B2, and B3) before and after hepatectomy. These HBox genes are considered to correlate with the process of liver regeneration.

Amino Acid Sequence↗
PubMed1983

Regeneration and the immune system. II. Suppressor activities of lymphocytes activated in vivo by liver regeneration and their genetic control.

The lymph node cells (LNC) activated in vivo by liver regeneration following partial hepatectomy of mice (primed lymph node cells) respond to regenerating liver cells in vitro with typical secondary immune response characteristics (Miyahara, S. et al., Eur. J. Immunol. 1983. 13: 878). These LNC activated in vivo suppress the proliferation of responder lymphocytes cultured with mitomycin C-treated regenerating syngeneic liver cells (sMLHLR). The suppressive activity was already present in LNC 4 days after partial hepatectomy and remained unchanged for at least 16 days. These primed LNC were effective not only on sMLHLR but also on syngeneic mixed lymphocyte culture (sMLR) and allogeneic mixed lymphocyte culture, of which responder cells share the I-A (I-B) subregions of the major histocompatibility complex (MHC) with primed LNC. At least one cell in the suppressor circuit is a T cell. The primed LNC restimulates in vitro with regenerating liver cells (in vitro reactivated primed LNC) suppressed the proliferation of syngeneic responder cells in sMLR, but not of cells from congeneic mice differing from the in vitro reactivated primed LNC at a cluster of genes linked to the Ig locus. Thus the suppressive activity of primed LNC is controlled by the I-A (I-B) subregions of the MHC and that of in vitro reactivated primed LNC by genes in the Ig region. The role of these suppressive cells in liver regeneration is discussed.

Animals↗
PubMed1980

Membrane potential measurements during rat liver regeneration.

Membrane potential was measured in perfused rat liver and was shown to increase from -33 +/- 1.0 mV in livers from normal rats to -50 +/- 1.1 mV in livers from rats 12 hr after partial hepatectomy. The hyperpolarization of the membrane in regenerating liver was no longer evident after perfusion with 1 mM ouabain for 5 min. Ouabain had a small (4 mV) depolarizing effect on membrane potential in normal liver. The potential measured in normal and regenerating liver decreased as a function of the external potassium concentration above 5 mM; however, the potential was more electronegative in regenerating liver compared to normal liver at all values of external potassium concentration, and the differences in potential between the two kinds of cells did not decrease at higher concentrations of external potassium. Thus, a plot of membrane potential vs external potassium concentration resulted in approximately parallel curves for the two different cell types. We conclude that hyperpolarization of the liver cell membrane is an early event during rat liver regeneration and results from an electrogenic Na-K pump.

Animals↗
PubMed1994

Altered levels of prothymosin immunoreactive peptide, a growth-related gene product, during liver regeneration after chronic ethanol feeding.

Liver regeneration is regulated by the orderly activation of growth-related genes. Although ethanol impairs induction of liver regeneration by partial hepatectomy, we have not identified ethanol-associated differences in the hepatic mRNA levels of several proto-oncogenes, including c-myc, which peaks 3-6 hr post-partial hepatectomy. Prothymosin alpha, a gene encoding a ubiquitous nuclear protein, is activated by c-myc in resting fibroblasts and has been implicated as a regulator of cell proliferation. Prothymosin alpha mRNA levels reportedly increase 12-32 hr post-partial hepatectomy, several hours after c-myc induction. We sought to determine if chronic ethanol intake alters the expected induction post-partial hepatectomy of prothymosin alpha steady-state mRNA expression and protein levels. Comparing rats chronically fed ethanol with pair-fed controls, we found no significant differences in steady-state levels of prothymosin alpha mRNA; however, we did see a delay in the increase of prothymosin immunoreactive peptide in rats chronically fed alcohol. This suggests that the inhibition in protein levels in ethanol fed rats is not due to lower steady-state mRNA levels, but may occur post-transcriptionally. Further data are needed to determine if this finding is important in the inhibition in cell growth following partial hepatectomy in rats chronically fed ethanol.

Alcoholism↗
PubMed1983

Impairment of liver regeneration during inhibition of mitochondrial protein synthesis by oxytetracycline.

Under standard conditions, liver regeneration is impaired if mitochondrial protein synthesis is completely blocked. By treating rats with oxytetracycline for various periods of time directly prior to partial hepatectomy, livers were led to a condition of relative deficiency in cytochrome c oxidase and ATP synthetase. To this end, oxytetracycline was administered by means of continuous intravenous infusion up to concentrations of 20 micrograms/ml serum, giving a gradual decrease in cytochrome c oxidase activity. This activity was used as a marker for functionally capable mitochondria and as a tool to monitor the efficiency of inhibition of mitochondrial protein synthesis. It is shown that liver regeneration is strongly impaired after a period of pretreatment of 22 days or more and continuation of oxytetracycline treatment during regeneration. The mitochondrial respiratory capacity is reduced to 14% of the control value under these conditions. To obtain inhibitory levels within the regenerating liver, it was necessary to raise the serum levels slightly above 20 micrograms/ml. This measure is most likely required because of the poor vascularization of the regenerating liver. The serum levels were kept, however, far below those known to inhibit cytoplasmic protein synthesis. The results show that in normal liver the respiratory capacity must be reduced drastically before energy-requiring processes become affected. In Zajdela hepatoma cells, similar effects are found after reduction of the cytochrome c oxidase activity to 38%. This difference in sensitivity is probably based on the different mitochondrial content of liver cells and the liver-derived Zajdela cells.

ATP Synthetase Complexes↗
PubMed1993

Transforming growth factor beta gene expression is transiently enhanced at a critical stage during liver regeneration after CCl4 treatment.

BACKGROUND: Transforming growth factor beta 1 (TGF beta 1) gene expression is increased in CCl4-injured rat livers. The biologic link of this increase and liver regeneration has not been established. EXPERIMENTAL DESIGN: To explore the identity of the TGF beta 1-producing cells in the CCl4 regenerating liver, we hybridized untreated and CCl4-treated liver sections of TGF beta 1-specific riboprobes and immunolocalized TGF beta 1 protein, simultaneously. To assess the dynamics of cellular proliferation during hepatic regeneration, chronologic changes in the cellular DNA synthesis were also monitored by [3H]thymidine incorporation and autoradiography. In situ hybridization analyses were further extended by subfractionation of nonparenchymal cells into Kupffer cells/macrophages, endothelial and Ito cells, and determining TGF beta 1 mRNA levels in different cell types. Finally, we experimentally tested if the temporal relationship between the transient elevation of expression of TGF beta 1 and hepatic cell proliferation were casually related. RESULTS: We observed that the rate of DNA synthesis was the highest around 36 hours post-treatment and preceded the time of enhanced accumulation of TGF beta 1 transcripts and protein, both of which peaked at approximately 48 hours and declined thereafter. Transient upregulation of TGF beta 1 gene expression was seen in the inflammatory cell infiltrates around the central vein and at less extent, in portal tracts, and in perisinusoidal cells near the zone of necrosis. Like TGF beta 1 transcripts, TGF beta 1 protein was also predominantly co-localized in and around the pericentral and periportal cells. Kupffer cells, that accumulate abundantly in the liver 48 hours after CCl4 administration, were the primary producers of TGF beta 1. The injection of neutralizing anti-TGF beta 1 antibodies into animals prevented both the decline in [3H]thymidine incorporation and cell division in the waning phases of hepatic regeneration at 72 hours. CONCLUSIONS: Based on our observations that (i) TGF beta 1 gene expression is triggered transiently during a crucial phase of liver regeneration, (ii) the exogenously added TGF beta 1 inhibits hepatic DNA synthesis and that (iii) the administration of TGF beta 1 antibodies extends the proliferative response of the regenerating liver, we conclude that TGF beta 1 plays a pivotal role in down regulating liver regeneration.

Animals↗
PubMed1983

Vasopressin modulates liver regeneration in the Brattleboro rat.

Liver regeneration following partial hepatectomy is significantly impaired in rats with hereditary vasopressin deficiency (Brattleboro strain), both in rate of DNA synthesis and in return of liver DNA content to normal. Vasopressin treatment at physiological doses ameliorates the defect and thus appears to be an important modulator of liver regeneration in response to partial hepatectomy in the rat.

Animals↗
PubMed1997

The in vivo effect of hepatotrophic factors augmenter of liver regeneration, hepatocyte growth factor, and insulin-like growth factor-II on liver natural killer cell functions.

Fine balanced sequential changes of the levels of circulating hepatotrophic factors are essential for normal liver regeneration. Our recent studies have indicated that liver-resident natural killer (NK) cells are important regulators of liver regeneration and have raised the possibility that hepatotrophic factors might mediate their activities through NK cells. In the present study, we assessed the effects of in vivo administration of three hepatotrophic factors (augmenter of liver regeneration [ALR], insulin-like growth factor-II [IGF-II], and hepatocyte growth factor [HGF]) on NK cells in normal rats. Each of the three, given over a 1-day period in doses known to produce hepatotrophic activity, induced inhibition of NK cell cytotoxic activities in the population of mononuclear leukocytes (MNL) in the liver, but not in MNL from the spleen or peripheral blood. In contrast to these results obtained by the whole animal treatment, the three molecules had no effect on NK cell functions when added to cultures of MNL from the livers, spleens, or blood of untreated rats. These data support and extend our previously advanced hypothesis that ALR and other hepatotrophic factors play an important role in liver regeneration by regional regulation of NK cells through some as-yet-unknown intermediary mechanism.

Animals↗
PubMed2005

Interplay among cardiotrophin-1, prostaglandins, and vascular endothelial growth factor in rat liver regeneration.

Prostaglandins are hepatoprotective molecules generated in liver regeneration by the rapid induction of cyclooxygenase-2 (COX-2). Cardiotrophin-1 (CT-1) and vascular endothelial growth factor (VEGF) are other hepatoprotective mediators upregulated at 24 hours after partial hepatectomy. The interactions among these molecules during liver regeneration have not yet been defined. Here we show that rats subjected to partial hepatectomy treated with NS-398, a specific COX-2 inhibitor, exhibited cell cycle arrest, increased hepatocyte apoptosis, persistent extracellular signal-regulated kinase (ERK) 1/2 activation, and increased interleukin-6 production. These changes were associated with downregulation of CT-1 and COX-1 and altered pattern of VEGF expression. Administration of an adenovirus encoding CT-1 to NS-398-treated rats restituted normal levels of COX-1, prostaglandins, and VEGF in the liver after partial hepatectomy and restored normal liver regeneration. Furthermore, the stimulation of isolated rat hepatocytes with CT-1 increased COX-1, COX-2, and VEGF messenger RNAs and prostaglandin synthesis. Conversely, the addition of prostaglandin E1 to the culture increased CT-1 and VEGF production. In conclusion, COX-2 activation and production of prostaglandins soon after partial hepatectomy are essential requirements for hepatocyte proliferation and for the correct induction of both CT-1 and VEGF. CT-1 can restore liver regeneration after COX-2 inhibition by increasing VEGF, COX-1 expression, and prostaglandin synthesis.

Animals↗
PubMed2007

Expression patterns and action analysis of genes associated with inflammatory responses during rat liver regeneration.

AIM: To study the relationship between inflammatory response and liver regeneration (LR) at transcriptional level. METHODS: After partial hepatectomy (PH) of rats, the genes associated with inflammatory response were obtained according to the databases, and the gene expression changes during LR were checked by the Rat Genome 230 2.0 array. RESULTS: Two hundred and thirty-nine genes were associated with liver regeneration. The initial and total expressing gene numbers found in initiation phase (0.5-4 h after PH), G(0)/G(0) transition (4-6 h after PH), cell proliferation (6-66 h after PH), cell differentiation and structure-function reconstruction (66-168 h after PH) of liver regeneration were 107, 34, 126, 6 and 107, 92, 233, 145 respectively, showing that the associated genes were mainly triggered at the beginning of liver regeneration, and worked at different phases. According to their expression similarity, these genes were classified into 5 groups: only up-regulated, predominantly up-, only down-, predominantly down-, up- and down-, involving 92, 25, 77, 14 and 31 genes, respectively. The total times of their up- and down-regulated expression were 975 and 494, respectively, demonstrating that the expressions of the majority of genes were increased, and that of a few genes were decreased. Their time relevance was classified into 13 groups, showing that the cellular physiological and biochemical activities were staggered during liver regeneration. According to gene expression patterns, they were classified into 33 types, suggesting that the activities were diverse and complex during liver regeneration. CONCLUSION: Inflammatory response is closely associated with liver regeneration, in which 239 LR-associated genes play an important role.

Animals↗
PubMed1983

Turnover of ribosomal 28S and 18S rRNA during rat liver regeneration.

The turnover of 28S and 18S rRNA was studied in the course of 12 d after partial hepatectomy, including the proliferative (1st to 5th d) and post-proliferative (6th to 12th d) phases of liver regeneration. Turnover data, as the day-to-day rates of synthesis and degradation of 28S and 18S rRNA, were obtained by employing a suitable experimental procedure for the estimation of the increase of the amount of rRNA in the regenerating liver. It was found that 28S and 18S rRNA are accumulated into the cytoplasm and degraded at identical rates both in the proliferative and post-proliferative phases. The turnover of both rRNA moieties is markedly slower during the first 3 d of liver regeneration.

Animals↗
PubMed2005

Repression of cytochrome P450 activity in human hepatocytes in vitro by a novel hepatotrophic factor, augmenter of liver regeneration.

Pathological disorders of the liver were shown to be associated with an impairment of hepatic drug metabolism mediated in part by growth factors. Augmenter of liver regeneration (ALR) is a novel liver-specific hepatotrophic growth factor, whereas its action on cytochrome P450 (P450) metabolism is completely unknown. Application of ALR to primary human hepatocytes in vitro reduced P450 isoenzyme activities (1A2 and 2A6) in a dose-dependent manner. Time-course analysis revealed that the maximal inhibitory effect was reached after 24 to 72 h of exposure with 50 nM ALR. The reduction of basal activities upon ALR treatment was 35% for CYP1A2, 56% for CYP2A6, 18% for CYP2B6, and 45% for CYP2E1. Additionally, after induction of P450 with specific inducers, ALR revealed an inhibitory effect on the isoenzyme activities (CYP1A2, 41%; CYP2B6, 35%). Investigations of protein and mRNA expression of basal and induced CYP1A2 and CYP3A4 after ALR treatment by Western blotting and real-time reverse transcriptase-polymerase chain reaction, respectively, suggest a regulation on the transcriptional level. Furthermore, ALR treatment increased nuclear factor kB activity and reduced constitutive androstane receptor but not pregnane X receptor or aryl hydrocarbon receptor expression. In contrast, ALR revealed no effects on phase II reactions (glutathione/oxidized glutathione, UDP-glucuronyltransferase conjugation). Our results indicate that ALR, as a member of hepatotrophic factors, down-regulates basal and induced P450 in human liver and therefore cross-links growth signals to regulation of hepatic metabolism. These findings further imply a possible role of ALR in drug interactions during impaired hepatic function, whereas liver regeneration is triggered.

Cells, Cultured↗
PubMed1994

Increased expression of mRNA for hepatocyte growth factor-like protein during liver regeneration and inflammation.

To assess potential roles of hepatocyte growth factor-like (HGFL) protein as a growth factor and as a cytokine, we determined the expression of mRNA for (HGFL) protein during liver regeneration and inflammation. Expression of mRNA for HGFL protein in the regenerating liver was upregulated to 93% and 64% above controls at 1 h following partial hepatectomy and carbon tetrachloride treatment of rats, respectively. Similarly, rat liver mRNA for HGFL protein was upregulated to 78% above controls at 24 h after injection of thioglycollate (inducing activation of peritoneal macrophages) and to 118% at 48 h after injection of turpentine (inducing the acute phase response). These results support a potential role for HGFL protein in the early phase of liver regeneration and as an inflammatory mediator.

Animals↗
PubMed1992

Effects of 1-[(2-thiazolin-2-yl)amino]acetyl-4-(1,3-dithiol 2-ylidene)-2,3,4,5-tetrahydro-1H-1-benzazepin-3,5-dione hydrochloride (KF-14363) on liver regeneration and function of hepatic mitochondria in partially hepatectomized rats.

Effects of 1-[(2-Thiazolin-2-yl)amino]acetyl-4-(1,3-dithiol 2-ylidene)-2,3,4,5-tetrahydro-1H-1-benzazepin-3,5-dione hydrochloride (KF-14363), a hepatoprotective compound, on liver regeneration, liver nucleic acid levels, mitochondrial respiration activity and hepatic energy metabolism after partial hepatectomy (OPE) in rats were studied. The liver regeneration rate was significantly increased in rats administered 100 mg/kg of KF-14363 for 6 d as compared with the control group administered vehicle. The serum glucose level in rats administered 100 mg/kg of KF-14363 measured 3 h after OPE (OPE 3 h) was significantly higher than that in rats administered vehicle (group A) and the serum insulin level in the KF-14363 group was more than double that of group A. KF-14363 also significantly increased liver nucleic acid levels in OPE rats. In mitochondrial function experiments, KF-14363 (100 mg/kg) was orally administered 2 h after OPE. Three hours after OPE (1 h after KF-14363 administration), state 3 respiration was significantly higher in the OPE 3 h + KF-14363 group than in the OPE 3 h + water group. The adenosine diphosphate/oxygen (ADP/O) ratio was also significantly higher in the OPE 22 h (22 h after OPE) + KF-14363 group than in the OPE 22 h + water group. On hepatic energy metabolism, KF-14363 increased adenosine diphosphate and triphosphate levels. Total adenine nucleotide level in the OPE 3 h + KF-14363 group was significantly higher than that in the OPE 3 h + water group. Adenylate energy charge (AEC) was slightly decreased in the OPE 3 h + water group and significantly decreased in the OPE 22 h + water group than in the corresponding sham group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗