Faculty Opinions recommendation of Hepatic stellate cells and portal fibroblasts are the major cellular sources of collagens and lysyl oxidases in normal liver and early after injury.

2013 ◽  
Author(s):  
Steffen Gay
Keyword(s):  
Hepatic Stellate Cells ◽  
Normal Liver ◽  
Stellate Cells ◽  
Lysyl Oxidases ◽  
Portal Fibroblasts

scholarly journals Hepatic stellate cells and portal fibroblasts are the major cellular sources of collagens and lysyl oxidases in normal liver and early after injury

2013 ◽  
Vol 304 (6) ◽  
pp. G605-G614 ◽  
Author(s):  
Maryna Perepelyuk ◽  
Masahiko Terajima ◽  
Andrew Y. Wang ◽  
Penelope C. Georges ◽  
Paul A. Janmey ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Hepatic Stellate Cells ◽  
Large Strain ◽  
Liver Stiffness ◽  
Normal Liver ◽  
Stellate Cells ◽  
Matrix Proteins ◽  
Cross Linking ◽  
Duct Ligation ◽  
Portal Fibroblasts

Liver fibrosis is characterized by excessive deposition of extracellular matrix proteins by myofibroblasts derived from hepatic stellate cells and portal fibroblasts. Activation of these precursors to myofibroblasts requires matrix stiffness, which results in part from increased collagen cross-linking mediated by lysyl oxidase (LOX) family proteins. The aims of this study were to characterize the mechanical changes of early fibrosis, to identify the cells responsible for LOX production in early injury, and to determine which cells in normal liver produce collagens and elastins, which serve as substrates for LOXs early after injury. Hepatocytes and liver nonparenchymal cells were isolated from normal and early-injured liver and examined immediately for expression of LOXs and matrix proteins. We found that stellate cells and portal fibroblasts were the major cellular sources of fibrillar collagens and LOXs in normal liver and early after injury (1 day after bile duct ligation and 2 and 7 days after CCl4 injury). Activity assays using stellate cells and portal fibroblasts in culture demonstrated significant increases in LOX family enzymatic activity as cells became myofibroblastic. LOX family-mediated deoxypyridinoline and pyridinoline cross-links increased after CCl4-mediated injury. There was a significant association between liver stiffness (as quantified by the shear storage modulus G′) and deoxypyridinoline levels; increased deoxypyridinoline levels were also coincident with significantly increased elastic resistance to large strain deformations, consistent with increased cross-linking of the extracellular matrix. These data suggest a model in which the liver is primed to respond quickly to injury, activating potential mechanical feed-forward mechanisms.

Secretion of MCP-1/CCL2 by bile duct epithelia induces myofibroblastic transdifferentiation of portal fibroblasts

2006 ◽  
Vol 290 (4) ◽  
pp. G765-G771 ◽  
Author(s):  
Emma A. Kruglov ◽  
Rebecca A. Nathanson ◽  
Trong Nguyen ◽  
Jonathan A. Dranoff
Keyword(s):  
Bile Duct ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Functional Responses ◽  
Blocking Antibody ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein ◽  
Portal Fibroblasts ◽  
Expression Loss

Portal fibroblasts (PF) are fibrogenic liver cells distinct from hepatic stellate cells (HSC). Recent evidence suggests that PF may be important mediators of biliary fibrosis and cirrhosis. The cytokine monocyte chemoattractant protein-1 (MCP-1)/CCL2 is upregulated in biliary fibrosis by bile duct epithelia (BDE) and induces functional responses in HSC. Thus we hypothesized that release of MCP-1 may mediate biliary fibrosis. We report that PF express functional receptors for MCP-1 that are distinct from the receptor CCR2. MCP-1 induces proliferation, increase and redistribution of α-smooth muscle (α-SMA) expression, loss of the ectonucleotidase NTPDase2, and upregulation of α1-procollagen production in PF. BDE secretions induce α-SMA levels in PF, and this is inhibited by MCP-1 blocking antibody. Together, these data suggest that BDE regulate PF proliferation and myofibroblastic transdifferentiation in a paracrine fashion via release of MCP-1.

scholarly journals Characterization of hepatic stellate cells, portal fibroblasts, and mesothelial cells in normal and fibrotic livers

2016 ◽  
Vol 64 (5) ◽  
pp. 1137-1146 ◽  
Author(s):  
Ingrid Lua ◽  
Yuchang Li ◽  
Jessica A. Zagory ◽  
Kasper S. Wang ◽  
Samuel W. French ◽  
...  
Keyword(s):  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Mesothelial Cells ◽  
Portal Fibroblasts

scholarly journals Fibrotic liver has prompt recovery after ischemia-reperfusion injury

2020 ◽  
Vol 318 (3) ◽  
pp. G390-G400 ◽  
Author(s):  
Takanori Konishi ◽  
Rebecca M. Schuster ◽  
Holly S. Goetzman ◽  
Charles C. Caldwell ◽  
Alex B. Lentsch
Keyword(s):  
Progenitor Cells ◽  
Hepatic Stellate Cells ◽  
Ischemia Reperfusion ◽  
Normal Liver ◽  
Stellate Cells ◽  
Hepatocyte Proliferation ◽  
Fibrotic Liver ◽  
Diseased Liver ◽  
Liver Repair ◽  
Macrophage Accumulation

Hepatic ischemia-reperfusion (I/R) is a major complication of liver resection, trauma, and liver transplantation; however, liver repair after I/R in diseased liver has not been studied. The present study sought to determine the manner in which the fibrotic liver repairs itself after I/R. Liver fibrosis was established in mice by CCl4 administration for 6 wk, and then liver I/R was performed to investigate liver injury and subsequent liver repair in fibrotic and control livers. After I/R, fibrotic liver had more injury compared with nonfibrotic, control liver; however, fibrotic liver showed rapid resolution of liver necrosis and reconstruction of liver parenchyma. Marked accumulation of hepatic stellate cells and macrophages were observed specifically in the fibrotic septa in early reparative phase. Fibrotic liver had higher numbers of hepatic stellate cells, macrophages, and hepatic progenitor cells during liver recovery after I/R than did control liver, but hepatocyte proliferation was unchanged. Fibrotic liver also had significantly greater number of phagocytic macrophages than control liver. Clodronate liposome injection into fibrotic mice after I/R caused decreased macrophage accumulation and delay of liver recovery. Conversely, CSF1-Fc injection into normal mice after I/R resulted in increased macrophage accumulation and concomitant decrease in necrotic tissue during liver recovery. In conclusion, fibrotic liver clears necrotic areas and restores normal parenchyma faster than normal liver after I/R. This beneficial response appears to be directly related to the increased numbers of nonparenchymal cells, particularly phagocytic macrophages, in the fibrotic liver. NEW & NOTEWORTHY This study is the first to reveal how diseased liver recovers after ischemia-reperfusion (I/R) injury. Although it was not completely unexpected that fibrotic liver had increased hepatic injury after I/R, a novel finding was that fibrotic liver had accelerated recovery and repair compared with normal liver. Enhanced repair after I/R in fibrotic liver was associated with increased expansion of phagocytic macrophages, hepatic stellate cells, and progenitor cells.

scholarly journals The role of Mesothelin signaling in Portal Fibroblasts in the pathogenesis of cholestatic liver fibrosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Hiroaki Fuji ◽  
Grant Miller ◽  
Takahiro Nishio ◽  
Yukinori Koyama ◽  
Kevin Lam ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Liver Injury ◽  
Hepatic Stellate Cells ◽  
Inflammatory Responses ◽  
Stellate Cells ◽  
Collagen Type I ◽  
Type I ◽  
Fibrotic Liver ◽  
Portal Fibroblasts

Liver fibrosis develops in response to chronic toxic or cholestatic injury, and is characterized by apoptosis of damaged hepatocytes, development of inflammatory responses, and activation of Collagen Type I producing myofibroblasts that make liver fibrotic. Two major cell types, Hepatic Stellate Cells (HSCs) and Portal Fibroblasts (PFs) are the major source of hepatic myofibroblasts. Hepatotoxic liver injury activates Hepatic Stellate Cells (aHSCs) to become myofibroblasts, while cholestatic liver injury activates both aHSCs and Portal Fibroblasts (aPFs). aPFs comprise the major population of myofibroblasts at the onset of cholestatic injury, while aHSCs are increasingly activated with fibrosis progression. Here we summarize our current understanding of the role of aPFs in the pathogenesis of cholestatic fibrosis, their unique features, and outline the potential mechanism of targeting aPFs in fibrotic liver.

Bile Acids and Stellate Cells

2015 ◽  
Vol 33 (3) ◽  
pp. 332-337 ◽  
Author(s):  
Claus Kordes ◽  
Iris Sawitza ◽  
Silke Götze ◽  
Dieter Häussinger
Keyword(s):  
Liver Regeneration ◽  
Bile Acids ◽  
Hepatic Stellate Cells ◽  
Normal Liver ◽  
Stellate Cells ◽  
Hepatic Differentiation ◽  
Liver And Pancreas ◽  
And Function

Hepatic stellate cells are mainly known for their contribution to fibrogenesis in chronic liver diseases, but their identity and function in normal liver remain unclear. They were recently identified as liver-resident mesenchymal stem cells (MSCs), which can differentiate not only into adipocytes and osteocytes, but also into liver epithelial cells such as hepatocytes and bile duct cells as investigated in vitro and in vivo. During hepatic differentiation, stellate cells and other MSCs transiently develop into liver progenitor cells with epithelial characteristics before hepatocytes are established. Transplanted stellate cells from the liver and pancreas are able to contribute to liver regeneration in stem cell-based liver injury models and can also home into the bone marrow, which is in line with their classification as MSCs. There is experimental evidence that bile acids support liver regeneration and are able to activate signaling pathways in hepatic stellate cells. For this reason, it is important to analyze the influence of bile acids on developmental fate decisions of hepatic stellate cells and other MSC populations.

Activated hepatic stellate cells and portal fibroblasts contribute to cholestatic liver fibrosis in MDR2 knockout mice

2019 ◽  
Vol 71 (3) ◽  
pp. 573-585 ◽  
Author(s):  
Takahiro Nishio ◽  
Ronglin Hu ◽  
Yukinori Koyama ◽  
Shuang Liang ◽  
Sara B. Rosenthal ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Knockout Mice ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Activated Hepatic Stellate Cells ◽  
Portal Fibroblasts

scholarly journals Endoglin Trafficking/Exosomal Targeting in Liver Cells Depends on N-Glycosylation

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 997 ◽  
Author(s):  
Meurer ◽  
Wimmer ◽  
Leur ◽  
Weiskirchen
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Hepatic Stellate Cells ◽  
Transforming Growth Factor ◽  
Stellate Cells ◽  
Transforming Growth Factor Β ◽  
Liver Cells ◽  
Type I ◽  
Caveolin 1 ◽  
Portal Fibroblasts ◽  
Opposing Effects

Injury of the liver involves a wound healing partial reaction governed by hepatic stellate cells and portal fibroblasts. Individual members of the transforming growth factor-β (TGF-β) superfamily including TGF-β itself and bone morphogenetic proteins (BMP) exert diverse and partially opposing effects on pro-fibrogenic responses. Signaling by these ligands is mediated through binding to membrane integral receptors type I/type II. Binding and the outcome of signaling is critically modulated by Endoglin (Eng), a type III co-receptor. In order to learn more about trafficking of Eng in liver cells, we investigated the membranal subdomain localization of full-length (FL)-Eng. We could show that FL-Eng is enriched in Caveolin-1-containing sucrose gradient fractions. Since lipid rafts contribute to the pool of exosomes, we could consequently demonstrate for the first time that exosomes isolated from cultured primary hepatic stellate cells and its derivatives contain Eng. Moreover, via adenoviral overexpression, we demonstrate that all liver cells have the capacity to direct Eng to exosomes, irrespectively whether they express endogenous Eng or not. Finally, we demonstrate that block of N-glycosylation does not interfere with dimerization of the receptor, but abrogates the secretion of soluble Eng (sol-Eng) and prevents exosomal targeting of FL-Eng.

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