scholarly journals Endothelial cells secreted endothelin-1 augments diabetic nephropathy via inducing extracellular matrix accumulation of mesangial cells in ETBR-/- mice

Aging ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1804-1820 ◽  
Author(s):  
Hong-hong Zou ◽  
Li Wang ◽  
Xiao-xu Zheng ◽  
Gao-si Xu ◽  
Yunfeng Shen
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Diabetic Nephropathy ◽  
Mesangial Cells ◽  
Endothelin 1 ◽  
Matrix Accumulation

scholarly journals Fractalkine and its receptor mediate extracellular matrix accumulation in diabetic nephropathy in mice

Diabetologia ◽  
2013 ◽  
Vol 56 (7) ◽  
pp. 1661-1669 ◽  
Author(s):  
K. H. Song ◽  
J. Park ◽  
J. H. Park ◽  
R. Natarajan ◽  
H. Ha
Keyword(s):  
Extracellular Matrix ◽  
Diabetic Nephropathy ◽  
Matrix Accumulation

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.

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