scholarly journals Effects of TJN-101, a lignan compound isolated from Schisandra fruits, on liver fibrosis and on liver regeneration after partial hepatectomy in rats with chronic liver injury induced by CCl4.

1987 ◽  
Vol 90 (1) ◽  
pp. 51-65 ◽  
Author(s):  
Shigefumi TAKEDA ◽  
Yoshio KASE ◽  
Ichiro ARAI ◽  
Yasufumi OHKURA ◽  
Masayuki HASEGAWA ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Liver Injury ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Chronic Liver ◽  
Chronic Liver Injury ◽  
Schisandra Fruits

scholarly journals Mechanisms of platelet-mediated liver regeneration

Blood ◽  
2016 ◽  
Vol 128 (5) ◽  
pp. 625-629 ◽  
Author(s):  
Ton Lisman ◽  
Robert J. Porte
Keyword(s):  
Liver Injury ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Therapeutic Strategies ◽  
Chronic Liver ◽  
Chronic Liver Injury ◽  
Multiple Functions ◽  
Definitive Evidence

Abstract Platelets have multiple functions beyond their roles in thrombosis and hemostasis. Platelets support liver regeneration, which is required after partial hepatectomy and acute or chronic liver injury. Although it is widely assumed that platelets stimulate liver regeneration by local excretion of mitogens stored within platelet granules, definitive evidence for this is lacking, and alternative mechanisms deserve consideration. In-depth knowledge of mechanisms of platelet-mediated liver regeneration may lead to new therapeutic strategies to treat patients with failing regenerative responses.

Blocking development of liver fibrosis augments hepatic progenitor cell‐derived liver regeneration in a mouse chronic liver injury model

2019 ◽  
Vol 49 (9) ◽  
pp. 1034-1045 ◽  
Author(s):  
Mitsuteru Kitade ◽  
Kosuke Kaji ◽  
Norihisa Nishimura ◽  
Kenichiro Seki ◽  
Keisuke Nakanishi ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Liver Injury ◽  
Liver Regeneration ◽  
Progenitor Cell ◽  
Chronic Liver ◽  
Hepatic Progenitor Cell ◽  
Chronic Liver Injury ◽  
Injury Model

scholarly journals Mesenchymal Stem Cells Transplantation following Partial Hepatectomy: A New Concept to Promote Liver Regeneration—Systematic Review of the Literature Focused on Experimental Studies in Rodent Models

2017 ◽  
Vol 2017 ◽  
pp. 1-22 ◽  
Author(s):  
Ioannis G. Papanikolaou ◽  
Charalambos Katselis ◽  
Konstantinos Apostolou ◽  
Themistoklis Feretis ◽  
Maria Lymperi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Failure ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Chronic Liver ◽  
Review Of The Literature ◽  
Chronic Liver Injury ◽  
Stem Cells Transplantation

Mesenchymal stem cells (MSCs) are an attractive source for regenerative medicine because they are easily accessible through minimally invasive methods and have the potential to enhance liver regeneration (LG) and improve liver function, following partial hepatectomy (PH) and acute or chronic liver injury. A systematic review of the literature was conducted for articles published up to September 1st, 2016, using the MEDLINE database. The keywords that were used in various combinations were as follows: “Mesenchymal stem cells”, “transplantation”, “stem cells”, “adipose tissue derived stem cells”, “bone marrow-derived stem cells”, “partial hepatectomy”, “acute liver failure”, “chronic liver failure”, “liver fibrosis”, “liver cirrhosis”, “rats”, “mice”, and “liver regeneration”. All introduced keywords were searched for separately in MeSH Database to control relevance and terminological accuracy and validity. A total of 41 articles were identified for potential inclusion and reviewed in detail. After a strict selection process, a total of 28 articles were excluded, leaving 13 articles to form the basis of this systematic review. MSCs transplantation promoted LG and improved liver function. Furthermore, MSCs had the ability to differentiate in hepatocyte-like cells, increase survival, and protect hepatocytes by paracrine mechanisms. MSCs transplantation may provide beneficial effects in the process of LG after PH and acute or chronic liver injury. They may represent a new therapeutic option to treat posthepatectomy acute liver failure.

Gab1 in livers with persistent hepatocyte apoptosis has an antiapoptotic effect and reduces chronic liver injury, fibrosis and tumorigenesis

2021 ◽  
Author(s):  
Tetsuo Takehara ◽  
Naoki Mizutani ◽  
Hayato Hikita ◽  
Yoshinobu Saito ◽  
Yuta Myojin ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Liver Injury ◽  
Cell Viability ◽  
Liver Regeneration ◽  
Adaptor Protein ◽  
Chronic Liver ◽  
Hepatocyte Apoptosis ◽  
Chronic Liver Injury ◽  
The Impact

Grb2-associated binder 1 (Gab1) is an adaptor protein that is important for intracellular signal transduction by receptor tyrosine kinases that are receptors for various growth factors and plays an important role in rapid liver regeneration after partial hepatectomy and during acute hepatitis. On the other hand, mild liver regeneration is induced in livers of individuals with chronic hepatitis, where hepatocyte apoptosis is persistent; however, the impact of Gab1 on such livers remains unclear. We examined the role of Gab1 in chronic hepatitis. Gab1 knockdown enhanced the decrease in cell viability and apoptosis induced by ABT-737, a Bcl-2/-xL/-w inhibitor, in BNL.CL2 cells, while cell viability and caspase activity were unchanged in the absence of ABT-737. ABT-737 treatment induced Gab1 cleavage to form p35-Gab1. p35-Gab1 was also detected in the livers of mice with hepatocyte-specific Mcl-1 knockout (KO), which causes persistent hepatocyte apoptosis. Gab1 deficiency exacerbated hepatocyte apoptosis in Mcl-1 KO mice with posttranscriptional downregulation of Bcl-XL. In BNL.CL2 cells treated with ABT-737, Gab1 knockdown posttranscriptionally suppressed Bcl-xL expression, and p35-Gab1 overexpression enhanced Bcl-xL expression. Gab1 deficiency in Mcl-1 KO mice activated STAT3 signaling in hepatocytes, increased hepatocyte proliferation, and increased the incidence of liver cancer with the exacerbation of liver fibrosis. In conclusion, Gab1 is cleaved in the presence of apoptotic stimuli and forms p35-Gab1 in hepatocytes. In chronic liver injury, the role of Gab1 in suppressing apoptosis and reducing liver damage, fibrosis, and tumorigenesis is more important than its role in liver regeneration.

Cellular Mechanisms of Tissue Fibrosis. 5. Novel insights into liver fibrosis

2013 ◽  
Vol 305 (8) ◽  
pp. C789-C799 ◽  
Author(s):  
Ariane Mallat ◽  
Sophie Lotersztajn
Keyword(s):  
Liver Fibrosis ◽  
Liver Injury ◽  
Cell Injury ◽  
Parenchymal Cell ◽  
Chronic Liver ◽  
Special Focus ◽  
Chronic Liver Injury ◽  
Cellular Mechanisms ◽  
Extracellular Matrix Components ◽  
Liver Fibrogenesis

Liver fibrosis is the common scarring reaction associated with chronic liver injury that results from prolonged parenchymal cell injury and/or inflammation. The fibrogenic response is characterized by progressive accumulation of extracellular matrix components enriched in fibrillar collagens and a failure of matrix turnover. This process is driven by a heterogeneous population of hepatic myofibroblasts, which mainly derive from hepatic stellate cells and portal fibroblasts. Regression of fibrosis can be achieved by the successful control of chronic liver injury, owing to termination of the fibrogenic reaction following clearance of hepatic myofibroblasts and restoration of fibrolytic pathways. Understanding of the complex network underlying liver fibrogenesis has allowed the identification of a large number of antifibrotic targets, but no antifibrotic drug has as yet been approved. This review will highlight recent advances regarding the mechanisms that regulate liver fibrogenesis and fibrosis regression, with special focus on novel signaling pathways and the role of inflammatory cells. Translation of these findings to therapies will require continued efforts to develop multitarget therapeutic approaches that will improve the grim prognosis of liver cirrhosis.

scholarly journals Liver fibrosis is driven by protease‐activated receptor‐1 expressed by hepatic stellate cells in experimental chronic liver injury

2020 ◽  
Vol 4 (5) ◽  
pp. 906-917
Author(s):  
Lauren G. Poole ◽  
Asmita Pant ◽  
Holly M. Cline‐Fedewa ◽  
Kurt J. Williams ◽  
Bryan L. Copple ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Liver Injury ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Chronic Liver ◽  
Chronic Liver Injury ◽  
Protease Activated Receptor 1

scholarly journals Hepatic Stellate Cell–Macrophage Crosstalk in Liver Fibrosis and Carcinogenesis

2020 ◽  
Vol 40 (03) ◽  
pp. 307-320
Author(s):  
Michitaka Matsuda ◽  
Ekihiro Seki
Keyword(s):  
Liver Fibrosis ◽  
Liver Injury ◽  
Cell Activation ◽  
Stellate Cell ◽  
Tumor Development ◽  
Mesenchymal Cell ◽  
Chronic Liver ◽  
Health Concern ◽  
Chronic Liver Injury ◽  
Fibrotic Liver

AbstractChronic liver injury due to viral hepatitis, alcohol abuse, and metabolic disorders is a worldwide health concern. Insufficient treatment of chronic liver injury leads to fibrosis, causing liver dysfunction and carcinogenesis. Most cases of hepatocellular carcinoma (HCC) develop in the fibrotic liver. Pathological features of liver fibrosis include extracellular matrix (ECM) accumulation, mesenchymal cell activation, immune deregulation, and angiogenesis, all of which contribute to the precancerous environment, supporting tumor development. Among liver cells, hepatic stellate cells (HSCs) and macrophages play critical roles in fibrosis and HCC. These two cell types interplay and remodel the ECM and immune microenvironment in the fibrotic liver. Once HCC develops, HCC-derived factors influence HSCs and macrophages to switch to protumorigenic cell populations, cancer-associated fibroblasts and tumor-associated macrophages, respectively. This review aims to summarize currently available data on the roles of HSCs and macrophages in liver fibrosis and HCC, with a focus on their interaction.

LC3-associated phagocytosis protects against inflammation and liver fibrosis via immunoreceptor inhibitory signaling

2020 ◽  
Vol 12 (539) ◽  
pp. eaaw8523 ◽  
Author(s):  
JingHong Wan ◽  
Emmanuel Weiss ◽  
Sanae Ben Mkaddem ◽  
Morgane Mabire ◽  
Pierre-Marie Choinier ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Liver Injury ◽  
Systemic Inflammation ◽  
Multiorgan Failure ◽  
Chronic Liver ◽  
Human Monocytes ◽  
Macrophage Phenotype ◽  
Chronic Liver Injury ◽  
Inflammatory Profile ◽  
Inhibitory Signaling

Sustained hepatic and systemic inflammation, particularly originating from monocytes/macrophages, is a driving force for fibrosis progression to end-stage cirrhosis and underlies the development of multiorgan failure. Reprogramming monocyte/macrophage phenotype has emerged as a strategy to limit inflammation during chronic liver injury. Here, we report that LC3-associated phagocytosis (LAP), a noncanonical form of autophagy, protects against hepatic and systemic inflammation during chronic liver injury in rodents, with beneficial antifibrogenic effects. LAP is enhanced in blood and liver monocytes from patients with fibrosis and cirrhosis. Pharmacological inhibition of LAP components in human monocytes from patients with cirrhosis or genetic disruption of LAP in mice with chronic liver injury exacerbates both the inflammatory signature in isolated human monocytes and the hepatic inflammatory profile in mice, resulting in enhanced liver fibrosis. Mechanistically, patients with cirrhosis showed increased monocyte expression of Fc fragment of IgG receptor IIA (FcγRIIA) and enhanced engulfment of immunoglobulin G in LC3+ phagosomes that triggers an FcγRIIA/Src homology region 2 domain–containing phosphatase-1 (SHP-1) inhibitory immunoreceptor tyrosine-based activation motif (ITAMi) anti-inflammatory pathway. Mice overexpressing human FcγRIIA in myeloid cells show enhanced LAP in response to chronic liver injury and resistance to inflammation and liver fibrosis. Activation of LAP is lost in monocytes from patients with multiorgan failure and restored by specifically targeting ITAMi signaling with anti-FcγRIIA F(ab′)2 fragments, or with intravenous immunoglobulin (IVIg). These data suggest the existence of an ITAMi-mediated mechanism by which LAP might protect against inflammation. Sustaining LAP may open therapeutic perspectives for patients with chronic liver disease.

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