Regulation of hepatocyte proliferation

1984 ◽  
Vol 71 (8) ◽  
pp. 404-407 ◽  
Author(s):  
G. Ruhenstroth-Bauer ◽  
M. Goldberg ◽  
S. Vogl
Keyword(s):  
Hepatocyte Proliferation

Hepatocyte proliferation after partial hepatectomy in absence of NF-κB activation

2001 ◽  
Vol 120 (5) ◽  
pp. A359-A359
Author(s):  
S LAURENT ◽  
C SEMPOUX ◽  
Y HORMANS ◽  
L LAMBOTTE
Keyword(s):  
Partial Hepatectomy ◽  
Hepatocyte Proliferation

scholarly journals F4/80+ Kupffer Cell-Derived Oncostatin M Sustains the Progression Phase of Liver Regeneration through Inhibition of TGF-β2 Pathway

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2231
Author(s):  
Qingjun Lu ◽  
Hao Shen ◽  
Han Yu ◽  
Jing Fu ◽  
Hui Dong ◽  
...  
Keyword(s):  
Liver Regeneration ◽  
Serum Levels ◽  
Inhibitory Effect ◽  
Regenerative Process ◽  
Oncostatin M ◽  
Hepatocyte Proliferation ◽  
Initiation Phase ◽  
Distinct Role

The role of Kupffer cells (KCs) in liver regeneration is complicated and controversial. To investigate the distinct role of F4/80+ KCs at the different stages of the regeneration process, two-thirds partial hepatectomy (PHx) was performed in mice to induce physiological liver regeneration. In pre- or post-PHx, the clearance of KCs by intraperitoneal injection of the anti-F4/80 antibody (α-F4/80) was performed to study the distinct role of F4/80+ KCs during the regenerative process. In RNA sequencing of isolated F4/80+ KCs, the initiation phase was compared with the progression phase. Immunohistochemistry and immunofluorescence staining of Ki67, HNF-4α, CD-31, and F4/80 and Western blot of the TGF-β2 pathway were performed. Depletion of F4/80+ KCs in pre-PHx delayed the peak of hepatocyte proliferation from 48 h to 120 h, whereas depletion in post-PHx unexpectedly led to persistent inhibition of hepatocyte proliferation, indicating the distinct role of F4/80+ KCs in the initiation and progression phases of liver regeneration. F4/80+ KC depletion in post-PHx could significantly increase TGF-β2 serum levels, while TGF-βRI partially rescued the impaired proliferation of hepatocytes. Additionally, F4/80+ KC depletion in post-PHx significantly lowered the expression of oncostatin M (OSM), a key downstream mediator of interleukin-6, which is required for hepatocyte proliferation during liver regeneration. In vivo, recombinant OSM (r-OSM) treatment alleviated the inhibitory effect of α-F4/80 on the regenerative progression. Collectively, F4/80+ KCs release OSM to inhibit TGF-β2 activation, sustaining hepatocyte proliferation by releasing a proliferative brake.

scholarly journals Keratin 7 expression in hepatic cholestatic diseases

2021 ◽  
Author(s):  
S. Sakellariou ◽  
C. Michaelides ◽  
T. Voulgaris ◽  
J. Vlachogiannakos ◽  
E. Manesis ◽  
...  
Keyword(s):  
Bile Duct ◽  
Inverse Correlation ◽  
Bile Duct Obstruction ◽  
Hepatocyte Proliferation ◽  
Primary Biliary Cholangitis ◽  
Specific Marker ◽  
Ductular Reaction ◽  
Duct Obstruction ◽  
Cholestatic Diseases ◽  
Keratin 7

AbstractWe evaluated keratin 7 (K7) hepatocellular expression in 92 patients with common types of acute and chronic cholestatic diseases caused by bile duct obstruction/destruction or parenchymal lesions [acute hepatitis (n=20), mixed/pure cholestasis (n=16), primary biliary cholangitis-PBC (n=35), primary sclerosing cholangitis-PSC (n=10), vanishing bile duct syndrome (n=3), complete large bile duct obstruction due to space-occupying lesions (n=8)]. K7 immunohistochemical hepatocellular expression and ductular reaction (DR) were semi-quantitatively assessed. Results were correlated with liver enzyme serum levels, cholestasis type, histological features, hepatocellular Ki67 labelling index (LI) and HepPar1 expression. Hepatocellular K7 expression was detected in 87% (81/92) cases and in all cholestatic disease types with lowest incidence in pure/mixed cholestasis and highest in incomplete bile duct obstruction (iBDO), reaching 100% in PSC. K7-positive hepatocytes had low Ki67 LI (0-5%) retaining HepPar1 expression, irrespective of disease type. PSC cases had high K7 hepatocellular expression even with intact bile ducts, a feature that may aid differential diagnosis of cholestatic syndromes. K7 hepatocellular expression significantly correlated with cholestasis type, bile duct loss and fibrosis stage. It was higher in milder acute cholestatic hepatitis showing inverse correlation with hepatocyte proliferation and serum transaminase levels. In iBDO, younger age independently correlated with high K7 expression, while serum GGT levels showed a nearly significant correlation. Correlation with DR findings implied that K7-positive hepatocytes may result through metaplasia. In conclusion, K7 hepatocellular expression is a sensitive though non-specific marker of cholestasis. It may represent a cytoprotective reaction of resting hepatocytes in cholestasis of longer duration especially in younger patients.

LINC00265 maintains hepatocyte proliferation during liver regeneration by targeting miRNA-28-5p

2021 ◽  
Vol 85 (3) ◽  
pp. 528-536
Author(s):  
Sheng Yu ◽  
Zhonglin Cui ◽  
Jie Zhou ◽  
Kai Wang ◽  
Qingping Li ◽  
...  
Keyword(s):  
Liver Resection ◽  
Liver Regeneration ◽  
Therapeutic Option ◽  
Weight Ratio ◽  
Hepatocyte Proliferation ◽  
Phase Cell ◽  
Luciferase Reporter ◽  
Hepatocyte Regeneration ◽  
M Phase ◽  
Reporter Assays

ABSTRACT Long noncoding RNAs have been implicated in many biological processes, but their roles in liver regeneration still need to be illustrated. Therefore, we aimed to investigate the role of LINC00265 as a pivotal regulator of hepatocyte proliferation during liver regeneration. It was found that LINC00265 is significantly upregulated in rat liver tissues at various time points after 2/3 liver resection. LINC00265 knockdown inhibited hepatocyte proliferation, induced cell apoptosis and led to G2/M phase cell cycle arrestment. In rats subjected to surgery, LINC00265 knockdown decreased liver/body weight ratio, attenuated improvement from liver damage and reduced Ki67 and PCNA expression. Luciferase reporter assays confirmed that miR-28-5p was a direct target of LINC00265, and inhibition of miR-28-5p abolished the effect of LINC00265 knockdown. In summary, LINC00265 might maintain hepatocyte proliferation by targeting miR-28-5p during liver regeneration and should be considered as a promising therapeutic option for hepatocyte regeneration after liver resection.

scholarly journals Bid agonist regulates murine hepatocyte proliferation by controlling endoplasmic reticulum calcium homeostasis

Hepatology ◽  
2010 ◽  
Vol 52 (1) ◽  
pp. 338-348 ◽  
Author(s):  
Hong-Min Ni ◽  
Catherine J. Baty ◽  
Na Li ◽  
Wen-Xing Ding ◽  
Wentao Gao ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Calcium Homeostasis ◽  
Hepatocyte Proliferation ◽  
Endoplasmic Reticulum Calcium ◽  
Murine Hepatocyte

scholarly journals Constitutive expression of cyclo-oxygenase 2 transgene in hepatocytes protects against liver injury

2008 ◽  
Vol 416 (3) ◽  
pp. 337-346 ◽  
Author(s):  
Rafael Mayoral ◽  
Belen Mollá ◽  
Juana Maria Flores ◽  
Lisardo Boscá ◽  
Marta Casado ◽  
...  
Keyword(s):  
Liver Injury ◽  
Transgenic Mice ◽  
Genetic Model ◽  
Acute Liver Injury ◽  
Constitutive Expression ◽  
Transgenic Animals ◽  
Hepatocyte Proliferation ◽  
Nuclear Antigen ◽  
Cox 2 ◽  
Inflammatory Profile

The effect of COX (cyclo-oxygenase)-2-dependent PGs (prostaglandins) in acute liver injury has been investigated in transgenic mice that express human COX-2 in hepatocytes. We have used three well-established models of liver injury: in LPS (lipopolysaccharide) injury in D-GalN (D-galactosamine)-preconditioned mice; in the hepatitis induced by ConA (concanavalin A); and in the proliferation of hepatocytes in regenerating liver after PH (partial hepatectomy). The results from the present study demonstrate that PG synthesis in hepatocytes decreases the susceptibility to LPS/D-GalN or ConA-induced liver injury as deduced by significantly lower levels of the pro-inflammatory profile and plasmatic aminotransferases in transgenic mice, an effect suppressed by COX-2-selective inhibitors. These Tg (transgenic) animals express higher levels of anti-apoptotic proteins and exhibit activation of proteins implicated in cell survival, such as Akt and AMP kinase after injury. The resistance to LPS/D-GalN-induced liver apoptosis involves an impairment of procaspase 3 and 8 activation. Protection against ConA-induced injury implies a significant reduction in necrosis. Moreover, hepatocyte commitment to start replication is anticipated in Tg mice after PH, due to the expression of PCNA (proliferating cell nuclear antigen), cyclin D1 and E. These results show, in a genetic model, that tissue-specific COX-2-dependent PGs exert an efficient protection against acute liver injury by an antiapoptotic/antinecrotic effect and by accelerated early hepatocyte proliferation.

scholarly journals Stem cell factor and c-kit are involved in hepatic recovery after acetaminophen-induced liver injury in mice

2008 ◽  
Vol 295 (1) ◽  
pp. G45-G53 ◽  
Author(s):  
Bin Hu ◽  
Lisa M. Colletti
Keyword(s):  
Stem Cell ◽  
Liver Injury ◽  
Stem Cell Factor ◽  
Cellular Proliferation ◽  
Hepatocyte Proliferation ◽  
Mrna Levels ◽  
Wild Type ◽  
Hepatocyte Apoptosis ◽  
Large Reservoir ◽  
A Cell

Stem cell factor (SCF) and its receptor c-kit are important in hematopoiesis and cellular proliferation. c-kit has also been identified as a cell surface marker for progenitor cells. We have previously shown that there is a large reservoir of hepatic SCF, and this molecule plays a significant role in liver regeneration after 70% hepatectomy. In the current study, we further examined the expression of SCF and c-kit in acetaminophen (APAP)-induced liver injury in C57BL/6J mice or SCF-deficient sl-sld mice and their appropriate wild-type controls. Following APAP-induced liver injury, c-kit mRNA expression increased, with peak levels detected 48 h postinjury. Hepatic SCF mRNA levels after APAP injury were also increased, with peak levels seen 16 h post-APAP. The mortality rate in SCF-deficient mice treated with APAP was significantly higher than that of wild-type mice; furthermore, administration of exogenous SCF significantly reduced the mortality of APAP-treated wild-type mice. Bromodeoxyuridine incorporation experiments showed that SCF significantly increased hepatocyte proliferation at 48 and 72 h in APAP-treated mice. SCF inhibited APAP-induced hepatocyte apoptosis and increased Bcl-2 and Bcl-xL expression, suggesting that this decrease in hepatocyte apoptosis is mediated through Bcl-2 and Bcl-xL. In summary, SCF and c-kit expression was increased after APAP-induced liver injury. Administration of exogenous SCF reduces mortality in APAP-treated mice, increases hepatocyte proliferation, and prevents hepatocyte apoptosis induced by APAP, suggesting that these molecules are important in the liver's recovery from these injuries.

scholarly journals Macrophage colony-stimulating factor increases hepatic macrophage content, liver growth, and lipid accumulation in neonatal rats

2018 ◽  
Vol 314 (3) ◽  
pp. G388-G398 ◽  
Author(s):  
Clare Pridans ◽  
Kristin A. Sauter ◽  
Katharine M. Irvine ◽  
Gemma M. Davis ◽  
Lucas Lefevre ◽  
...  
Keyword(s):  
Birth Weight ◽  
Low Birth Weight ◽  
Kupffer Cell ◽  
Lipid Accumulation ◽  
Cell Expansion ◽  
Somatic Growth ◽  
Hepatocyte Proliferation ◽  
Neonatal Rats ◽  
Colony Stimulating Factor ◽  
Stimulating Factor

Signaling via the colony-stimulating factor 1 receptor (CSF1R) controls the survival, differentiation, and proliferation of macrophages. Mutations in CSF1 or CSF1R in mice and rats have pleiotropic effects on postnatal somatic growth. We tested the possible application of pig CSF1-Fc fusion protein as a therapy for low birth weight (LBW) at term, using a model based on maternal dexamethasone treatment in rats. Neonatal CSF1-Fc treatment did not alter somatic growth and did not increase the blood monocyte count. Instead, there was a substantial increase in the size of liver in both control and LBW rats, and the treatment greatly exacerbated lipid droplet accumulation seen in the dexamethasone LBW model. These effects were reversed upon cessation of treatment. Transcriptional profiling of the livers supported histochemical evidence of a large increase in macrophages with a resident Kupffer cell phenotype and revealed increased expression of many genes implicated in lipid droplet formation. There was no further increase in hepatocyte proliferation over the already high rates in neonatal liver. In conclusion, treatment of neonatal rats with CSF1-Fc caused an increase in liver size and hepatic lipid accumulation, due to Kupffer cell expansion and/or activation rather than hepatocyte proliferation. Increased liver macrophage numbers and expression of endocytic receptors could mitigate defective clearance functions in neonates.NEW & NOTEWORTHY This study is based on extensive studies in mice and pigs of the role of CSF1/CSF1R in macrophage development and postnatal growth. We extended the study to neonatal rats as a possible therapy for low birth weight. Unlike our previous studies in mice and pigs, there was no increase in hepatocyte proliferation and no increase in monocyte numbers. Instead, neonatal rats treated with CSF1 displayed reversible hepatic steatosis and Kupffer cell expansion.

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