Impaired proliferation of non-parenchymal cells participates in an impairment of liver regeneration in db/db mice

2005 ◽  
Vol 79 (1) ◽  
pp. 51-58 ◽  
Author(s):  
Koji Uetsuka ◽  
Makoto Shirai ◽  
Hirofumi Yamauchi ◽  
Hiroyuki Nakayama ◽  
Kunio Doi
Keyword(s):  
Liver Regeneration ◽  
Parenchymal Cells

scholarly journals Participation of 5-lipoxygenase and LTB4 in liver regeneration after partial hepatectomy

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Florencia Lorenzetti ◽  
Marina Cecilia Vera ◽  
María Paula Ceballos ◽  
María Teresa Ronco ◽  
Gerardo Bruno Pisani ◽  
...  
Keyword(s):  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Time Course ◽  
Specific Inhibitor ◽  
Ph Control ◽  
Initial Time ◽  
Male Wistar Rats ◽  
The Moment ◽  
Parenchymal Cells ◽  
The Impact

AbstractRegeneration is the unmatched liver ability for recovering its functional mass after tissue lost. Leukotrienes (LT) are a family of eicosanoids with the capacity of signaling to promote proliferation. We analyzed the impact of blocking LT synthesis during liver regeneration after partial hepatectomy (PH). Male Wistar rats were subjected to two-third PH and treated with zileuton, a specific inhibitor of 5-lipoxygenase (5-LOX). Our first find was a significant increment of intrahepatic LTB4 during the first hour after PH together with an increase in 5-LOX expression. Zileuton reduced hepatic LTB4 levels at the moment of hepatectomy and also inhibited the increase in hepatic LTB4. This inhibition produced a delay in liver proliferation as seen by decreased PCNA and cyclin D1 nuclear expression 24 h post-PH. Results also showed that hepatic LTB4 diminution by zileuton was associated with a decrease in NF-ĸB activity. Additionally, decreased hepatic LTB4 levels by zileuton affected the recruitment of neutrophils and macrophages. Non-parenchymal cells (NPCs) from zileuton-treated PH-rats displayed higher apoptosis than NPCs from PH control rats. In conclusion, the present work provides evidences that 5-LOX activation and its product LTB4 are involved in the initial signaling events for liver regeneration after PH and the pharmacological inhibition of this enzyme can delay the initial time course of the phenomenon.

scholarly journals MicroRNA-21 is upregulated during the proliferative phase of liver regeneration, targets Pellino-1, and inhibits NF-κB signaling

2010 ◽  
Vol 298 (4) ◽  
pp. G535-G541 ◽  
Author(s):  
Rebecca T. Marquez ◽  
Erik Wendlandt ◽  
Courtney Searcey Galle ◽  
Kathy Keck ◽  
Anton P. McCaffrey
Keyword(s):  
Liver Regeneration ◽  
Cultured Cells ◽  
Inverse Correlation ◽  
Luciferase Reporter ◽  
Mrna Levels ◽  
Messenger Rnas ◽  
Early Stages ◽  
Small Regulatory Rnas ◽  
Reporter Assays ◽  
Parenchymal Cells

During liver regeneration, normally quiescent liver cells reenter the cell cycle, nonparenchymal and parenchymal cells divide, and proper liver architecture is restored. The gene expression programs regulating these transitions are not completely understood. MicroRNAs are a newly discovered class of small regulatory RNAs that silence messenger RNAs by binding to their 3′-untranslated regions (UTRs). A number of microRNAs, including miR-21, have been shown to be involved in regulation of cell proliferation. We performed partial hepatectomies on mice and allowed the liver to regenerate for 1, 6, 12, 24, and 48 h and 4 and 7 days. We compared the expression of miR-21 in the posthepatectomy liver to the prehepatectomy liver by Northern blot and found that miR-21 was upregulated during the early stages of liver regeneration. NF-κB signaling is also activated very early during liver regeneration. It has been previously reported that NF-κB upregulates the miR-21 precursor transcript. The predicted miR-21 target, Pellino ( Peli1), is a ubiquitin ligase involved in activating NF-κB signaling. We observed an inverse correlation between miR-21 and Peli1 mRNA levels during liver regeneration. miR-21 overexpression in cultured cells inhibited a Peli1 3′-UTR luciferase reporter. Using NF-κB reporter assays, we determined that miR-21 overexpression inhibits NF-κB signaling. In conclusion, miR-21 expression was upregulated during early stages of liver regeneration. Targeting of Peli1 by miR-21 could potentially provide the basis for a negative feedback cycle regulating NF-κB signaling.

scholarly journals Hemostasis and Liver Regeneration

2020 ◽  
Vol 46 (06) ◽  
pp. 735-742 ◽  
Author(s):  
Patrick Starlinger ◽  
James P. Luyendyk ◽  
Dafna J. Groeneveld
Keyword(s):  
Liver Regeneration ◽  
Liver Diseases ◽  
Hepatic Function ◽  
Liver Mass ◽  
Regenerative Capacity ◽  
Liver Remnant ◽  
Hemostatic System ◽  
Normal Hepatic Function ◽  
Complication Of Surgery ◽  
Parenchymal Cells

AbstractThe liver is unique in its remarkable regenerative capacity, which enables the use of liver resection as a treatment for specific liver diseases, including removal of neoplastic liver disease. After resection, the remaining liver tissue (i.e, liver remnant) regenerates to maintain normal hepatic function. In experimental settings as well as patients, removal of up to two-thirds of the liver mass stimulates a rapid and highly coordinated process resulting in the regeneration of the remaining liver. Mechanisms controlling the initiation and termination of regeneration continue to be discovered, and many of the fundamental signaling pathways controlling the proliferation of liver parenchymal cells (i.e., hepatocytes) have been uncovered. Interestingly, while hemostatic complications (i.e., bleeding and thrombosis) are primarily thought of as a complication of surgery itself, strong evidence suggests that components of the hemostatic system are, in fact, powerful drivers of liver regeneration. This review focuses on the clinical and translational evidence supporting a link between the hemostatic system and liver regeneration, and the mechanisms whereby the hemostatic system directs liver regeneration discovered using experimental settings.

scholarly journals Hepatic non-parenchymal cells and extracellular matrix participate in oval cell-mediated liver regeneration

2009 ◽  
Vol 15 (5) ◽  
pp. 552 ◽  
Author(s):  
Wei Zhang ◽  
Xiao-Ping Chen ◽  
Wan-Guang Zhang ◽  
Feng Zhang ◽  
Shuai Xiang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Liver Regeneration ◽  
Oval Cell ◽  
Parenchymal Cells

scholarly journals TREM-2 defends the liver against hepatocellular carcinoma through multifactorial protective mechanisms

Gut ◽  
2020 ◽  
pp. gutjnl-2019-319227 ◽  
Author(s):  
Aitor Esparza-Baquer ◽  
Ibone Labiano ◽  
Omar Sharif ◽  
Aloña Agirre-Lizaso ◽  
Fiona Oakley ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Regeneration ◽  
Protective Role ◽  
Hepatocyte Proliferation ◽  
Protective Mechanisms ◽  
Liver Tumours ◽  
Parenchymal Cells ◽  
Antioxidant Diet ◽  
The Impact

ObjectiveHepatocellular carcinoma (HCC) is a prevalent and aggressive cancer usually arising on a background of chronic liver injury involving inflammatory and hepatic regenerative processes. The triggering receptor expressed on myeloid cells 2 (TREM-2) is predominantly expressed in hepatic non-parenchymal cells and inhibits Toll-like receptor signalling, protecting the liver from various hepatotoxic injuries, yet its role in liver cancer is poorly defined. Here, we investigated the impact of TREM-2 on liver regeneration and hepatocarcinogenesis.DesignTREM-2 expression was analysed in liver tissues of two independent cohorts of patients with HCC and compared with control liver samples. Experimental HCC and liver regeneration models in wild type and Trem-2-/- mice, and in vitro studies with hepatic stellate cells (HSCs) and HCC spheroids were conducted.ResultsTREM-2 expression was upregulated in human HCC tissue, in mouse models of liver regeneration and HCC. Trem-2-/- mice developed more liver tumours irrespective of size after diethylnitrosamine (DEN) administration, displayed exacerbated liver damage, inflammation, oxidative stress and hepatocyte proliferation. Administering an antioxidant diet blocked DEN-induced hepatocarcinogenesis in both genotypes. Similarly, Trem-2-/- animals developed more and larger tumours in fibrosis-associated HCC models. Trem-2-/- livers showed increased hepatocyte proliferation and inflammation after partial hepatectomy. Conditioned media from human HSCs overexpressing TREM-2 inhibited human HCC spheroid growth in vitro through attenuated Wnt ligand secretion.ConclusionTREM-2 plays a protective role in hepatocarcinogenesis via different pleiotropic effects, suggesting that TREM-2 agonism should be investigated as it might beneficially impact HCC pathogenesis in a multifactorial manner.

340 Sorafenib Treatment Inhibits Non-Parenchymal Cells After 2/3 Partial Hepatectomy in Mice, but Does Not Impair Liver Regeneration

2010 ◽  
Vol 138 (5) ◽  
pp. S-784
Author(s):  
Fredrik Johansson ◽  
Javier Vaquero ◽  
Jordi Bruix ◽  
Nelson Fausto ◽  
Jean Campbell
Keyword(s):  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Sorafenib Treatment ◽  
Parenchymal Cells

scholarly journals Hepatic stellate cells contribute to liver regeneration through galectins in hepatic stem cell niche

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jian-Yun Ge ◽  
Yun-Wen Zheng ◽  
Tomonori Tsuchida ◽  
Kinji Furuya ◽  
Hiroko Isoda ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Liver Regeneration ◽  
Stem Cell Niche ◽  
Hepatic Stem Cells ◽  
Hepatic Stem Cell ◽  
Gene And Protein Expression ◽  
Forming Efficiency ◽  
Cell Niche ◽  
Parenchymal Cells

Abstract Background As a critical cellular component in the hepatic stem cell niche, hepatic stellate cells (HSCs) play critical roles in regulating the expansion of hepatic stem cells, liver regeneration, and fibrogenesis. However, the signaling of HSCs, particularly that involved in promoting hepatic stem cell expansion, remains unclear. While the overexpression of galectins has been identified in regenerating liver tissues, their involvement in cell-cell interactions between HSCs and hepatic stem cells remains to be elucidated. Methods To generate a liver regeneration rat model and establish a hepatic oval cell microenvironment as a stem cell niche, 2-acetylaminofluorene treatment plus partial hepatectomy was performed. Immunofluorescence staining was conducted to detect the emergence of hepatic stem cells and their niche. Liver parenchymal cells, non-parenchymal cells, and HSCs were isolated for gene and protein expression analysis by qPCR or western blotting. To evaluate the effect of galectins on the colony-forming efficiency of hepatic stem cells, c-Kit−CD29+CD49f+/lowCD45−Ter-119− cells were cultured with recombinant galectin protein, galectin antibody, galectin-producing HSCs, and galectin-knockdown HSCs. Results Following liver injury, the cytokeratin 19+ ductal cells were robustly induced together with the emergence of OV6+CD44+CD133+EpCAM+ hepatic stem cells. The activated desmin+ HSCs were recruited around the periportal area and markedly enriched in the galectin-positive domain compared to the other non-parenchymal cells. Notably, the HSC fraction isolated from regenerating liver was accompanied by dramatically elevated gene and protein expression of galectins. Hepatic stem cells co-cultured with HSCs significantly enhanced colony-forming efficiency. Conversely, single or double knockdown of galectin-1 and galectin-3 led into a significant function loss, impaired the co-cultured hepatic stem cells to attenuated colony size, inhibited colony frequency, and reduced total cell numbers in colonies. On the other hand, the promotive function of galectins was further confirmed by recombinant galectin protein supplementation and galectins blocking antibodies. Conclusions Our findings, for the first time, demonstrated that galectins from activated HSCs contribute to hepatic stem cell expansion during liver regeneration, suggesting that galectins serve as important stem cell niche components.

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