scholarly journals Regulation of Fibrotic Processes in the Liver by ADAM Proteases

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1226 ◽  
Author(s):  
Dirk Schmidt-Arras ◽  
Stefan Rose-John
Keyword(s):  
Extracellular Matrix ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Present Review ◽  
Signalling Pathways ◽  
Receptor Interactions ◽  
The Future ◽  
Intercellular Signalling ◽  
Membrane Bound ◽  
Adam Family

Fibrosis in the liver is mainly associated with the activation of hepatic stellate cells (HSCs). Both activation and clearance of HSCs can be mediated by ligand–receptor interactions. Members of the a disintegrin and metalloprotease (ADAM) family are involved in the proteolytic release of membrane-bound ligands and receptor ectodomains and the remodelling of the extracellular matrix. ADAM proteases are therefore major regulators of intercellular signalling pathways. In the present review we discuss how ADAM proteases modulate pro- and anti-fibrotic processes and how ADAM proteases might be harnessed therapeutically in the future.

Cirrhotic extracellular matrix affects Hic-5 expression in primary human hepatic stellate cells

2020 ◽  
Vol 73 ◽  
pp. S299-S300
Author(s):  
Simona Onali ◽  
Elisabetta Caon ◽  
Kessarin Thanapirom ◽  
Martina Marrali ◽  
Maria Giovanna Vilia ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Hepatic Stellate Cells ◽  
Stellate Cells

scholarly journals Endothelin-1 in portal hypertension: The intricate role of hepatic stellate cells

2020 ◽  
Vol 245 (16) ◽  
pp. 1504-1512 ◽  
Author(s):  
Devaraj Ezhilarasan
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Portal Hypertension ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Chronic Liver ◽  
Liver Sinusoidal Endothelial Cells ◽  
Sinusoidal Endothelial Cells ◽  
Endothelin 1 ◽  
Activated Hepatic Stellate Cells

Portal hypertension is one of the most important cirrhosis-associated complications of chronic liver disease, leading to significant morbidity and mortality. After chronic liver injury, hepatic stellate cells reside in the perisinusoidal space activted and acquire a myofibroblast-like phenotype. The activated hepatic stellate cells act as both sources as well as the target for a potent vasoconstrictor endothelin-1. Activation of hepatic stellate cells plays a vital role in the onset of cirrhosis by way of increased extracellular matrix production and the enhanced contractile response to vasoactive mediators such as endothelin-1. In fibrotic/cirrhotic liver, activated hepatic stellate cells produce endothelin-1 leading to an imbalance between pro and antifibrotic factors responsible for enormous extracellular matrix synthesis. Thus, extracellular matrix deposition in the perisinusoidal space further augments liver stiffness and elevates the vascular tone and portal hypertension. Portal hypertension is a complex process modulated by several cell types like hepatic stellate cells, liver sinusoidal endothelial cells, Kupffer cells, injured hepatocytes, immune cells, and biliary epithelial cells. Therefore, targeting a single cell type may not be useful for regression of cirrhosis and portal hypertension. Nevertheless, numerous findings indicate that functionally liver sinusoidal endothelial cells and hepatic stellate cells closely regulate the sinusoidal blood flow via synthesis of several vasoactive molecules including endothelin-1, and hence targeting these cells with novel pharmacological agents may offer promising results. Impact statement Portal hypertension is pathologically defined as increase of portal venous pressure, mainly due to chronic liver diseases such as fibrosis and cirrhosis. In fibrotic liver, activated hepatic stellate cells increase their contraction in response to endothelin-1 (ET-1) via autocrine and paracrine stimulation from liver sinusoidal endothelial cells and injured hepatocytes. Clinical studies are limited with ET receptor antagonists in cirrhotic patients with portal hypertension. Hence, studies are needed to find molecules that block ET-1 synthesis. Accumulation of extracellular matrix proteins in the perisinusoidal space, tissue contraction, and alteration in blood flow are prominent during portal hypertension. Therefore, novel matrix modulators should be tested experimentally as well as in clinical studies. Specifically, tumor necrosis factor-α, transforming growth factor-β1, Wnt, Notch, rho-associated protein kinase 1 signaling antagonists, and peroxisome proliferator-activated receptor α and γ, interferon-γ and sirtuin 1 agonists should be tested elaborately against cirrhosis patients with portal hypertension.

scholarly journals Expression of cytokine and extracellular matrix mRNAs in fetal hepatic stellate cells

2017 ◽  
Vol 22 (9) ◽  
pp. 836-844 ◽  
Author(s):  
Keai Sinn Tan ◽  
Kasem Kulkeaw ◽  
Yoichi Nakanishi ◽  
Daisuke Sugiyama
Keyword(s):  
Extracellular Matrix ◽  
Hepatic Stellate Cells ◽  
Stellate Cells
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