scholarly journals Transitional Remodeling of the Hepatic Extracellular Matrix in Alcohol-Induced Liver Injury

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Lauren G. Poole ◽  
Gavin E. Arteel
Keyword(s):  
Extracellular Matrix ◽  
Liver Disease ◽  
Liver Injury ◽  
Primary Site ◽  
Alcohol Metabolism ◽  
Disease States ◽  
Ecm Proteins ◽  
Target Organs ◽  
Major Target

Alcohol consumption is a common custom worldwide, and the toxic effects of alcohol on several target organs are well understood. The liver is the primary site of alcohol metabolism and is therefore the major target of alcohol toxicity. Alcoholic liver disease is a spectrum of disease states, ranging from simple steatosis (fat accumulation), to inflammation, and eventually to fibrosis and cirrhosis if untreated. The fibrotic stage of ALD is primarily characterized by robust accumulation of extracellular matrix (ECM) proteins (collagens) which ultimately impairs the function of the organ. The role of the ECM in early stages of ALD is poorly understood, but recent research has demonstrated that a number of changes in the hepatic ECM in prefibrotic ALD not only are present, but may also contribute to disease progression. The purpose of this review is to summarize the established and proposed changes to the hepatic extracellular matrix (ECM) that may contribute to earlier stages of ALD development and to discuss potential mechanisms by which these changes may mediate the progression of the disease.

scholarly journals The Matrisome, Inflammation, and Liver Disease

2020 ◽  
Vol 40 (02) ◽  
pp. 180-188 ◽  
Author(s):  
Christine E. Dolin ◽  
Gavin E. Arteel
Keyword(s):  
Extracellular Matrix ◽  
Liver Disease ◽  
Fatty Liver ◽  
Chronic Liver Disease ◽  
Fatty Liver Disease ◽  
Chronic Liver ◽  
Disease Development ◽  
Disease States ◽  
Ecm Proteins

AbstractChronic fatty liver disease is common worldwide. This disease is a spectrum of disease states, ranging from simple steatosis (fat accumulation) to inflammation, and eventually to fibrosis and cirrhosis if untreated. The fibrotic stage of chronic liver disease is primarily characterized by robust accumulation of extracellular matrix (ECM) proteins (collagens) that ultimately impairs the function of the organ. The role of the ECM in early stages of chronic liver disease is less well-understood, but recent research has demonstrated that several changes in the hepatic ECM in prefibrotic liver disease are not only present but may also contribute to disease progression. The purpose of this review is to summarize the established and proposed changes to the hepatic ECM that may contribute to inflammation during earlier stages of disease development, and to discuss potential mechanisms by which these changes may mediate the progression of the disease.

scholarly journals The Role of Structural Extracellular Matrix Proteins in Urothelial Bladder Cancer (Review)

2007 ◽  
Vol 2 ◽  
pp. BMI.S294 ◽  
Author(s):  
Andrea Brunner ◽  
Alexandar Tzankov
Keyword(s):  
Extracellular Matrix ◽  
Cancer Cells ◽  
Cell Invasion ◽  
Matrix Proteins ◽  
Urothelial Bladder Cancer ◽  
Ecm Proteins ◽  
Cancer Review ◽  
Urothelial Bladder ◽  
Carcinoma Of The Bladder

The extracellular matrix (ECM) plays a key role in the modulation of cancer cell invasion. In urothelial carcinoma of the bladder (UC) the role of ECM proteins has been widely studied. The mechanisms, which are involved in the development of invasion, progression and generalization, are complex, depending on the interaction of ECM proteins with each other as well as with cancer cells. The following review will focus on the pathogenetic role and prognostic value of structural proteins, such as laminins, collagens, fibronectin (FN), tenascin (Tn-C) and thrombospondin 1 (TSP1) in UC. In addition the role of integrins mediating the interaction of ECM molecules and cancer cells will be addressed, since integrin-mediated FN, Tn-C and TSP1 interactions seem to play an important role during tumor cell invasion and angiogenesis.

Increased hepatic fibrosis and JNK2-dependent liver injury in mice exhibiting hepatocyte-specific deletion of cFLIP

2012 ◽  
Vol 303 (4) ◽  
pp. G498-G506 ◽  
Author(s):  
Jörn M. Schattenberg ◽  
Michael Nagel ◽  
Yong Ook Kim ◽  
Tobias Kohl ◽  
Marcus A. Wörns ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Injury ◽  
Chronic Liver Disease ◽  
Hepatic Fibrosis ◽  
Chronic Liver ◽  
Hepatocellular Injury ◽  
Inhibitory Protein ◽  
Hepatocellular Apoptosis ◽  
Specific Deletion

Chronic liver disease promotes hepatocellular injury involving apoptosis and triggers compensatory regeneration that leads to the activation of quiescent stellate cells in the liver. The deposition of extracellular matrix from activated myofibroblasts promotes hepatic fibrosis and the progression to cirrhosis with deleterious effects on liver physiology. The role of apoptosis signaling pathways in the development of fibrosis remains undefined. The aim of the current study was to determine the involvement of the caspase-8 homologue cellular FLICE-inhibitory protein (cFLIP) during the initiation and progression of fibrosis. Liver injury and fibrosis from carbon tetrachloride (CCl4) and thioacetamide (TAA) were examined in mice exhibiting a hepatocyte-specific deletion of cFLIP ( flip −/−). Acute liver injury from CCl4 and TAA were enhanced in flip −/− mice. This was accompanied by increased activation of caspase-3 and -9, pronounced phosphorylation of JNK, and decreased phosphorylation of Erk. Deletion of the cJun NH2-terminal kinase 2 (JNK2) in flip −/− mice protected from injury. Hepatic fibrosis was increased at baseline in 12-wk-old flip −/− mice, and progression of fibrosis from TAA was accelerated compared with the wild type. In conclusion, deletion of cFLIP in hepatocytes leads to increased fibrosis and accelerated fibrosis progression. This is accompanied by increased injury involving the activation of caspases and JNK2. Thus predisposition to liver injury involving increased hepatocellular apoptosis is a critical mediator of accelerated fibrogenesis, and prevention of liver injury will be a most important measure for patients with chronic liver disease.

scholarly journals Toll-Like Receptor 3 in Liver Diseases

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Shi Yin ◽  
Bin Gao
Keyword(s):  
Liver Disease ◽  
Liver Fibrosis ◽  
Liver Injury ◽  
Immune Cells ◽  
Liver Diseases ◽  
Human Liver ◽  
Toll Like Receptor ◽  
Double Stranded Rna ◽  
Nonparenchymal Cells

Toll-like receptor 3 (TLR3) is a member of the TLR family that can recognize double-stranded RNA (dsRNA), playing an important role in antiviral immunity. Recent studies have shown that TLR3 is also expressed on parenchymal and nonparenchymal cells in the liver as well as on several types of immune cells. In this review, we summarize the role of TLR3 in liver injury, inflammation, regeneration, and liver fibrosis, and discuss the implication of TLR3 in the pathogenesis of human liver diseases including viral hepatitis and autoimmune liver disease.

scholarly journals Fibrogénesis hepática células estelares hepáticas

Tequio ◽  
2018 ◽  
Vol 1 (2) ◽  
pp. 79-84
Author(s):  
Osiris G Ildefonso García ◽  
Alma Aurora Ramírez Hernández ◽  
Jovito César Santos Álvarez ◽  
Juan M Velázquez Enriquez ◽  
Gabriel Carrasco Torres ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Liver Disease ◽  
Liver Fibrosis ◽  
Chronic Liver Disease ◽  
Chronic Liver ◽  
Biliary Disease ◽  
Considerable Evidence ◽  
Insight Into

Liver fibrosis affects both the amount and the composition of the extracellular matrix. This process may occur during chronic liver disease characterized by hepato biliary disease or inflammation. There is now considerable evidence to support the role of the hepatic stellar cells (HSC) as the main matrix producing cells in fibrogenesis. The focus of this review is to provide insight into hepatic stellar cells in the fibrogenic process.

scholarly journals Cancer Cell-derived Secretory Factors in Breast Cancer-associated Lung Metastasis: Their Mechanism and Future Prospects

2020 ◽  
Vol 20 (3) ◽  
pp. 168-186 ◽  
Author(s):  
Tabinda Urooj ◽  
Bushra Wasim ◽  
Shamim Mushtaq ◽  
Syed Nudrat Nawaid Shah ◽  
Muzna Shah
Keyword(s):  
Breast Cancer ◽  
Extracellular Matrix ◽  
Cancer Cell ◽  
Lung Metastasis ◽  
Primary Site ◽  
Ecm Remodeling ◽  
Metastatic Cells ◽  
Extracellular Matrix Components ◽  
Matrix Components

: In Breast cancer, Lung is the second most common site of metastasis after the bone. Various factors are responsible for Lung metastasis occurring secondary to Breast cancer. Cancer cellderived secretory factors are commonly known as ‘Cancer Secretomes’. They exhibit a prompt role in the mechanism of Breast cancer lung metastasis. They are also major constituents of hostassociated tumor microenvironment. Through cross-talk between cancer cells and the extracellular matrix components, cancer cell-derived extracellular matrix components (CCECs) such as hyaluronan, collagens, laminin and fibronectin cause ECM remodeling at the primary site (breast) of cancer. However, at the secondary site (lung), tenascin C, periostin and lysyl oxidase, along with pro-metastatic molecules Coco and GALNT14, contribute to the formation of pre-metastatic niche (PMN) by promoting ECM remodeling and lung metastatic cells colonization. Cancer cell-derived secretory factors by inducing cancer cell proliferation at the primary site, their invasion through the tissues and vessels and early colonization of metastatic cells in the PMN, potentiate the mechanism of Lung metastasis in Breast cancer. : On the basis of biochemical structure, these secretory factors are broadly classified into proteins and non-proteins. This is the first review that has highlighted the role of cancer cell-derived secretory factors in Breast cancer Lung metastasis (BCLM). It also enumerates various researches that have been conducted to date in breast cancer cell lines and animal models that depict the prompt role of various types of cancer cell-derived secretory factors involved in the process of Breast cancer lung metastasis. In the future, by therapeutically targeting these cancer driven molecules, this specific type of organ-tropic metastasis in breast cancer can be successfully treated.

Alpha-1 antitrypsin governs alcohol-related liver disease in mice and humans

Gut ◽  
2020 ◽  
pp. gutjnl-2020-321375
Author(s):  
Christoph Grander ◽  
Benedikt Schaefer ◽  
Julian Schwärzler ◽  
Felix Grabherr ◽  
Dennis M de Graaf ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Liver Disease ◽  
Liver Injury ◽  
Serum Concentration ◽  
Neutrophil Infiltration ◽  
Serum Concentrations ◽  
Cox Regression Analysis ◽  
Alpha 1 Antitrypsin ◽  
Related Liver Disease

ObjectiveAlcohol-related liver disease (ALD) is a global healthcare problem with limited treatment options. Alpha-1 antitrypsin (AAT, encoded by SERPINA1) shows potent anti-inflammatory activities in many preclinical and clinical trials. In our study, we aimed to explore the role of AAT in ALD.DesignAn unselected cohort of 512 patients with cirrhosis was clinically characterised. Survival, clinical and biochemical parameters including AAT serum concentration were compared between patients with ALD and other aetiologies of liver disease. The role of AAT was evaluated in experimental ALD models.ResultsCirrhotic ALD patients with AAT serum concentrations less than 120 mg/dL had a significantly higher risk for death/liver transplantation as compared with patients with AAT serum concentrations higher than 120 mg/dL. Multivariate Cox regression analysis showed that low AAT serum concentration was a NaMELD-independent predictor of survival/transplantation. Ethanol-fed wild-type (wt) mice displayed a significant decline in hepatic AAT compared with pair-fed mice. Therefore, hAAT-Tg mice were ethanol-fed, and these mice displayed protection from liver injury associated with decreased steatosis, hepatic neutrophil infiltration and abated expression of proinflammatory cytokines. To test the therapeutic capability of AAT, ethanol-fed wt mice were treated with human AAT. Administration of AAT ameliorated hepatic injury, neutrophil infiltration and steatosis.ConclusionCirrhotic ALD patients with AAT concentrations less than 120 mg/dL displayed an increased risk for death/liver transplantation. Both hAAT-Tg mice and AAT-treated wt animals showed protection from ethanol-induced liver injury. AAT could reflect a treatment option for human ALD, especially for alcoholic hepatitis.

scholarly journals Differential expression of Lutheran/BCAM regulates biliary tissue remodeling in ductular reaction during liver regeneration

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Yasushi Miura ◽  
Satoshi Matsui ◽  
Naoko Miyata ◽  
Kenichi Harada ◽  
Yamato Kikkawa ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Injury ◽  
Critical Role ◽  
Disease Models ◽  
Distinct Mode ◽  
Ductular Reaction ◽  
Deficient Mice ◽  
Injured Liver

Under chronic or severe liver injury, liver progenitor cells (LPCs) of biliary origin are known to expand and contribute to the regeneration of hepatocytes and cholangiocytes. This regeneration process is called ductular reaction (DR), which is accompanied by dynamic remodeling of biliary tissue. Although the DR shows apparently distinct mode of biliary extension depending on the type of liver injury, the key regulatory mechanism remains poorly understood. Here, we show that Lutheran (Lu)/Basal cell adhesion molecule (BCAM) regulates the morphogenesis of DR depending on liver disease models. Lu+ and Lu- biliary cells isolated from injured liver exhibit opposite phenotypes in cell motility and duct formation capacities in vitro. By overexpression of Lu, Lu- biliary cells acquire the phenotype of Lu+ biliary cells. Lu-deficient mice showed severe defects in DR. Our findings reveal a critical role of Lu in the control of phenotypic heterogeneity of DR in distinct liver disease models.

Sign in / Sign up

Export Citation Format

Share Document