Spatio-Temporal Control of Hepatic Stellate Cell–Endothelial Cell Interactions for Reconstruction of Liver Sinusoids In Vitro

2012 ◽  
Vol 18 (9-10) ◽  
pp. 1045-1056 ◽  
Author(s):  
Junichi Kasuya ◽  
Ryo Sudo ◽  
Toshihiro Mitaka ◽  
Mariko Ikeda ◽  
Kazuo Tanishita
Keyword(s):  
Endothelial Cell ◽  
Hepatic Stellate Cell ◽  
Stellate Cell ◽  
Cell Interactions ◽  
Temporal Control ◽  
Liver Sinusoids ◽  
Spatio Temporal

Stiffness is associated with hepatic stellate cell heterogeneity during liver fibrosis

2021 ◽  
Author(s):  
Enis Kostallari ◽  
Bo Wei ◽  
Delphine Sicard ◽  
Jiahui Li ◽  
Shawna A. Cooper ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Focal Adhesion ◽  
Hepatic Stellate Cell ◽  
Stellate Cell ◽  
Liver Stiffness ◽  
Specific Protein ◽  
Cellular Level ◽  
Fibrotic Liver ◽  
Soft Matrix

The fibrogenic wound-healing response in liver increases stiffness. Stiffness mechano-transduction in turn amplifies fibrogenesis. Here, we aimed to understand the distribution of stiffness in fibrotic liver, how it impacts hepatic stellate cell (HSC) heterogeneity and identify mechanisms by which stiffness amplifies fibrogenic responses. Magnetic resonance elastography and atomic force microscopy demonstrated a heterogenous distribution of liver stiffness at macroscopic and microscopic levels, respectively, in a carbon tetrachloride (CCl4) mouse model of liver fibrosis as compared to controls. High stiffness was mainly attributed to extracellular matrix dense areas. To identify a stiffness-sensitive HSC sub-population, we performed scRNA-seq on primary HSCs derived from healthy versus CCl4-treated mice. A sub-cluster of HSCs was matrix-associated with the most upregulated pathway in this sub-population being focal adhesion signaling, including a specific protein termed four and a half LIM domains protein 2 (FHL2). In vitro, FHL2 expression was increased in primary human HSCs cultured on stiff matrix as compared to HSCs on soft matrix. Moreover, FHL2 knockdown inhibited fibronectin and collagen 1 expression, whereas its overexpression promoted matrix production. In summary, we demonstrate stiffness heterogeneity at the whole organ, lobular, and cellular level which drives an amplification loop of fibrogenesis through specific focal adhesion molecular pathways.

Preconditioning and adenosine in I/R-induced leukocyte-endothelial cell interactions

1998 ◽  
Vol 274 (4) ◽  
pp. H1230-H1238 ◽  
Author(s):  
Paul Kubes ◽  
Derrice Payne ◽  
Lena Ostrovsky
Keyword(s):  
Endothelial Cell ◽  
Leukocyte Adhesion ◽  
Vascular Dysfunction ◽  
Ischemia Reperfusion ◽  
Microvascular Dysfunction ◽  
Cell Interactions ◽  
Minor Role ◽  
Neutrophil Adhesion ◽  
Rolling Velocity

Recently, it was reported that preconditioning reduced leukocyte adhesion following ischemia-reperfusion (I/R). We further examined the effects of preconditioning and adenosine not only on neutrophil adhesion but also on neutrophil rolling and vascular dysfunction. Intravital microscopy revealed a decrease in neutrophil rolling velocity; a profound increase in neutrophil rolling, adhesion, and microvascular dysfunction; and a reduction in venular shear rates associated with 60 min ischemia and 60 min reperfusion in the feline mesentery. Preconditioning (5 min ischemia/10 min reperfusion) prevented subsequent I/R-induced slow neutrophil rolling, neutrophil adhesion, and microvascular dysfunction but did not affect the flux of rolling neutrophils. Adenosine deaminase A1and A2adenosine-receptor antagonists had only minor effects on the preconditioning responses. Pretreatment of vessels with exogenous adenosine reduced neutrophil adhesion and microvascular permeability and improved neutrophil rolling velocity and shear forces associated with I/R, but the flux of rolling neutrophils was not affected. Finally, in vitro experiments revealed that adenosine had absolutely no direct effect on neutrophil-endothelial cell interactions. In conclusion, our data suggest that adenosine plays only a minor role in preconditioned vessels and that adenosine per se may not directly affect neutrophil-endothelial cell interactions.

Ethanol enhances leukocyte-endothelial cell interactions in mesenteric venules

1990 ◽  
Vol 259 (4) ◽  
pp. G578-G583 ◽  
Author(s):  
P. R. Kvietys ◽  
M. A. Perry ◽  
T. S. Gaginella ◽  
D. N. Granger
Keyword(s):  
Endothelial Cell ◽  
Receptor Antagonist ◽  
Alcohol Intoxication ◽  
Leukotriene B4 ◽  
Cell Interactions ◽  
In Vivo Studies ◽  
Rolling Velocity ◽  
Neutrophil Adherence

In vivo studies have implicated neutrophils in the gastric mucosal injury produced by intraluminal administration of ethanol. However, in vitro studies indicate that ethanol inhibits various neutrophil functions such as adherence, chemotaxis, and degranulation. The aim of the present study was to assess whether ethanol, at clinically relevant concentrations, is proinflammatory in vivo. Ethanol (0.2, 1.0, 2.0, and 4.0%) was applied to the surface of the cat mesentery, and neutrophil adherence to venules (30 microns diam) and extravasation into the interstitium were quantitated using intravital microscopy. Hemodynamic parameters were also measured (venular diameter, red blood cell velocity, and leukocyte rolling velocity) or calculated (venular blood flow and wall shear stress). In this model ethanol produced a dose-dependent increase in neutrophil adherence and extravasation. The increase in leukocyte-endothelial cell interactions could not be attributed to alterations in hemodynamic factors. Pretreatment of animals with a monoclonal antibody (MoAb IB4) directed to the neutrophil CD11/CD18 adherence complex completely prevented the ethanol-induced neutrophil adherence and extravasation. Pretreatment with a leukotriene B4 (LTB4)-receptor antagonist (SC 41930) or a platelet-activating factor (PAF)-receptor antagonist (WEB 2170) did not alter the ethanol-induced neutrophil-endothelial interactions. We conclude that ethanol is proinflammatory at concentrations which may be achieved in the mucosal interstitium during acute alcohol intoxication. The ethanol-induced leukocyte adherence and extravasation is dependent on the expression of adhesive glycoproteins. The inflammatory mediators, PAF and LTB4, do not appear to play an important role in the leukocyte-endothelial cell interactions initiated by ethanol.

Characterization of microvascular cell cultures from normotensive and hypertensive rat brains: Pericyte—endothelial cell interactions in vitro

1987 ◽  
Vol 19 (2) ◽  
pp. 197-206 ◽  
Author(s):  
Ira M. Herman ◽  
Patricia M. Newcomb ◽  
John E. Coughlin ◽  
Stanley Jacobson
Keyword(s):  
Endothelial Cell ◽  
Cell Cultures ◽  
Cell Interactions ◽  
Hypertensive Rat

Hepatic Stellate Cell-Specific Gene Silencing Induced by an Artificial MicroRNA for Antifibrosis In Vitro

2009 ◽  
Vol 55 (3) ◽  
pp. 642-653 ◽  
Author(s):  
Ying Chang ◽  
Hua-jun Jiang ◽  
Xue-mei Sun ◽  
Xiao-kun Cai ◽  
Xing-xing He ◽  
...  
Keyword(s):  
Gene Silencing ◽  
Hepatic Stellate Cell ◽  
Stellate Cell ◽  
Specific Gene ◽  
Artificial Microrna
Sign in / Sign up

Export Citation Format

Share Document