scholarly journals Mechanotransduction in Liver Diseases

2019 ◽  
Vol 40 (01) ◽  
pp. 084-090 ◽  
Author(s):  
Ningling Kang
Keyword(s):  
Hepatic Stellate Cells ◽  
Liver Diseases ◽  
Cell Function ◽  
Stellate Cells ◽  
Basic Knowledge ◽  
Mechanical Forces ◽  
Biological Responses ◽  
A Cell ◽  
Portal Fibroblasts ◽  
External Forces

AbstractChronic liver diseases, such as fibrosis and cancer, lead to a rigid or stiff liver because of perpetual activation of hepatic stellate cells or portal fibroblasts into matrix-producing myofibroblasts. Mechanical forces, as determined by the mechanical properties of extracellular matrix or pressure of circulating blood flow/shear stress, are sensed by mechanoreceptors at the plasma membrane and transmitted into a cell to impact cell function. This process is termed as mechanotransduction. This review includes basic knowledge regarding how external forces are sensed, amplified, and transmitted into the interior of a cell as far as the nucleus to regulate gene transcription and generate biological responses. It also reviews literatures to highlight the mechanisms by which mechanical forces in a normal or diseased liver influence the phenotype of hepatocytes, hepatic stellate cells, portal fibroblasts, and sinusoidal endothelial cells, and these cells in turn participate in the initiation and progression of liver diseases.

scholarly journals Hepatic Stellate Cells Inhibit T Cells through Active TGF-β1 from a Cell Surface–Bound Latent TGF-β1/GARP Complex

2015 ◽  
Vol 195 (6) ◽  
pp. 2648-2656 ◽  
Author(s):  
Yan Li ◽  
Byung-Gyu Kim ◽  
Shiguang Qian ◽  
John J. Letterio ◽  
John J. Fung ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Surface ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
A Cell ◽  
Tgf Β1 ◽  
Garp Complex

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 The role of hepatic stellate cells in fibrotic liver diseases

2020 ◽  
Vol 35 (2) ◽  
pp. 113-118
Author(s):  
Hye Jin Cho ◽  
Jae Young Jang ◽  
Tae Min Kim
Keyword(s):  
Hepatic Stellate Cells ◽  
Liver Diseases ◽  
Stellate Cells ◽  
Fibrotic Liver

scholarly journals Hepatic Stellate Cell-Derived Microvesicles Prevent Hepatocytes from Injury Induced by APAP/H2O2

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Renwei Huang ◽  
Qunwen Pan ◽  
Xiaotang Ma ◽  
Yan Wang ◽  
Yaolong Liang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Hepatic Stellate Cells ◽  
Culture Medium ◽  
Caspase 3 ◽  
Cell Function ◽  
Stellate Cell ◽  
Annexin V ◽  
Stellate Cells ◽  
Human Hepatocytes ◽  
Injury Models

Hepatic stellate cells (HSCs), previously described for liver-specific mesenchymal stem cells (MSCs), appear to contribute to liver regeneration. Microvesicles (MVs) are nanoscale membrane fragments, which can regulate target cell function by transferring contents from their parent cells. The aim of this study was to investigate the effect of HSC-derived MVs on xenobiotic-induced liver injury. Rat and human hepatocytes, BRL-3A and HL-7702, were used to build hepatocytes injury models by n-acetyl-p-aminophenol n-(APAP) or H2O2treatment. MVs were prepared from human and rat HSCs, LX-2, and HST-T6 and, respectively, added to injured BRL-3A and HL-7702 hepatocytes. MTT assay was utilized to determine cell proliferation. Cell apoptosis was analyzed by flow cytometry and hoechst33258 staining. Western blot was used for analyzing the expression of activated caspase-3. Liver injury indicators, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) in culture medium were also assessed. Results showed that (1) HSC-MVs derived from LX-2 and HST-T6 were positive to CD90 and annexin V surface markers; (2) HSC-MVs dose-dependently improved the viability of hepatocytes in both injury models; (3) HSC-MVs dose-dependently inhibited the APAP/H2O2induced hepatocytes apoptosis and activated caspase-3 expression and leakage of LDH, ALT, and AST. Our results demonstrate that HSC-derived MVs protect hepatocytes from toxicant-induced injury.

scholarly journals Knockout of microRNA-21 attenuates alcoholic hepatitis through the VHL/NF-κB signaling pathway in hepatic stellate cells

2018 ◽  
Vol 315 (3) ◽  
pp. G385-G398 ◽  
Author(s):  
Nan Wu ◽  
Kelly McDaniel ◽  
Tianhao Zhou ◽  
Sugeily Ramos-Lorenzo ◽  
Chaodong Wu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Hepatic Stellate Cells ◽  
Liver Diseases ◽  
Cytokine Production ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Stellate Cells ◽  
Alcoholic Liver Injury ◽  
Human Hscs ◽  
Alcoholic Liver Diseases

microRNA-21 (miRNA) is one of the most abundant miRNAs in chronic liver injuries including alcoholic liver injury. Previous studies have demonstrated that miR-21 plays a role in inflammation in the liver and functions in hepatic stellate cells (HSCs), which reside in the perisinusoidal space between sinusoidal endothelial cells and hepatocytes and regulate sinusoidal circulation. HSCs integrate cytokine-mediated inflammatory responses in the sinusoids and relay them to the liver parenchyma. Here, we showed that the activation of Von Hippel-Lindau (VHL) expression, by miR-21 knockout in vivo and anti-miR-21 or VHL overexpression in vitro, suppressed the production of proinflammatory cytokines, such as interleukin (IL)-6, monocyte chemoattractant protein-1, and IL-1β, in human HSCs during alcoholic liver injury. Sequence and functional analyses confirmed that miR-21 directly targeted the 3′-untranslated region of VHL. Immunofluorescence and real-time PCR analysis revealed that miR-21 depletion blocked NF-κB activation in human HSCs both in cultured HSCs as well as HSCs isolated from alcohol-related liver disease mice liver by laser capture microdissection. We also showed that conditioned medium from anti-miR-21-transfected HSCs suppressed human monocyte-derived THP-1 cell migration. Taken together, our study indicates that depletion of miR-21 may downregulate cytokine production in HSCs and macrophage chemotaxis during alcoholic liver injury and that the targeting of miR-21 may have therapeutic potential for preventing the progression of alcoholic liver diseases. NEW & NOTEWORTHY This study demonstrates that silencing microRNA-21 can inhibit cytokine production and inflammatory responses in human hepatic stellate cells during alcoholic liver injury and that the targeting of microR-21 in hepatic stellate cells may have therapeutic potential for prevention and treatment of alcoholic liver diseases.

scholarly journals Prominent regulatory but weak antigen-presenting cell function of hepatic stellate cells

Hepatology ◽  
2011 ◽  
Vol 54 (3) ◽  
pp. 1108-1108 ◽  
Author(s):  
Frank A. Schildberg ◽  
Christian Kurts ◽  
Percy A. Knolle
Keyword(s):  
Hepatic Stellate Cells ◽  
Cell Function ◽  
Stellate Cells ◽  
Antigen Presenting Cell ◽  
Antigen Presenting

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
Sign in / Sign up

Export Citation Format

Share Document