scholarly journals Liver Fibrosis and Protection Mechanisms Action of Medicinal Plants Targeting Apoptosis of Hepatocytes and Hepatic Stellate Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Florent Duval ◽  
Jorge E. Moreno-Cuevas ◽  
Maria Teresa González-Garza ◽  
Carlos Rodríguez-Montalvo ◽  
Delia Elva Cruz-Vega
Keyword(s):  
Liver Fibrosis ◽  
Medicinal Plants ◽  
Cell Lines ◽  
Hepatic Stellate Cells ◽  
Alcohol Intake ◽  
Treatment Strategies ◽  
Stellate Cells ◽  
High Incidence ◽  
Protection Mechanisms

Following chronic liver injury, hepatocytes undergo apoptosis leading to activation of hepatic stellate cells (HSC). Consequently, activated HSC proliferate and produce excessive extracellular matrix, responsible for the scar formation. The pandemic trend of obesity, combined with the high incidence of alcohol intake and viral hepatitis infections, highlights the urgent need to find accessible antifibrotic therapies. Treatment strategies should take into account the versatility of its pathogenesis and act on all the cell lines involved to reduce liver fibrosis. Medicinal plants are achieving popularity as antifibrotic agents, supported by their safety, cost-effectiveness, and versatility. This review will describe the role of hepatocytes and HSC in the pathogenesis of liver fibrosis and detail the mechanisms of modulation of apoptosis of both cell lines by twelve known hepatoprotective plants in order to reduce liver fibrosis.

scholarly journals The Role of Signal Transducer and Activator of Transcription 5 and Transforming Growth Factor-β1 in Hepatic Fibrosis Induced by Chronic Hepatitis C Virus Infection in Egyptian Patients

2018 ◽  
Vol 27 (2) ◽  
pp. 115-121
Author(s):  
Mona A. Abu El Makarem ◽  
Ghada M. El-Sagheer ◽  
Moustafa A. Abu El-Ella
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Liver Fibrosis ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Serum Levels ◽  
Signal Transducer ◽  
Egyptian Patients ◽  
Tgf Β1

Objective: To investigate the possible role of signal transducer and activator of transcription 5 (STAT5) in the pathogenesis of liver fibrosis in Egyptian patients with chronic hepatitis C (CHC) virus infection and its relation to hepatic stellate cells (HSC). Subjects and Methods: Sixty-five patients (46 males and 19 females) were divided into 4 groups based on the severity of fibrosis as detected by Fibroscan as follows: F1, n = 15; F2, n = 21; F3, n = 13; and F4, n = 16. Twenty age- and gender-matched healthy persons volunteered as controls. The serum levels of STAT5, TGF-β1, α-smooth muscle actin (α-SMA), fasting blood sugar, and fasting insulin, as well as homeostasis model assessment of insulin resistance (HOMA-IR), were determined and compared for all groups. The usefulness of the studied serum biomarkers for predicting liver fibrosis was evaluated using a receiver operating characteristic curve. Results: Serum levels of STAT5 were significantly lower in patients compared to controls (9.69 ± 5.62 vs. 14.73 ± 6.52, p ≤ 0.001); on the contrary, TGF-β1, α-SMA, and HOMA-IR were significantly higher in patients compared to controls (mean: 1,796.04 vs. 1,636.94; 14.94 vs. 8.1; and 7.91 vs. 4.18; p ≤ 0.01 and 0.001, respectively). TGF-β1 and α-SMA showed a progressive increase with advancing severity of hepatic fibrosis (mean TGF-β1: 2,058.4 in F1-F2 and 1,583.8 in F3-F4, p ≤ 0.04; mean α-SMA: 13.59 in F1-F2 and 16.62 in F3-F4, p ≤ 0.05). STAT5 had a significant negative correlation with TGF-β1 (p ≤ 0.001), while no correlation was detected with α-SMA (p ≤ 0.8). Conclusions: STAT5 may play a significant role in hepatic fibrogenesis through the induction of TGF-β1 but not through the activation of hepatic stellate cells.

scholarly journals Inhibition of SIRT2 suppresses hepatic fibrosis

2016 ◽  
Vol 310 (11) ◽  
pp. G1155-G1168 ◽  
Author(s):  
Maribel Arteaga ◽  
Na Shang ◽  
Xianzhong Ding ◽  
Sherri Yong ◽  
Scott J. Cotler ◽  
...  
Keyword(s):  
Gene Expression ◽  
Liver Fibrosis ◽  
Hepatic Fibrosis ◽  
Hepatic Stellate Cells ◽  
Histone Deacetylases ◽  
Critical Role ◽  
Stellate Cells ◽  
Novel Strategy ◽  
Underlying Mechanisms

Liver fibrosis can progress to cirrhosis and result in serious complications of liver disease. The pathogenesis of liver fibrosis involves the activation of hepatic stellate cells (HSCs), the underlying mechanisms of which are not fully known. Emerging evidence suggests that the classic histone deacetylases play a role in liver fibrosis, but the role of another subfamily of histone deacetylases, the sirtuins, in the development of hepatic fibrosis remains unknown. In this study, we found that blocking the activity of sirtuin 2 (SIRT2) by using inhibitors or shRNAs significantly suppressed fibrogenic gene expression in HSCs. We further demonstrated that inhibition of SIRT2 results in the degradation of c-MYC, which is important for HSC activation. In addition, we discovered that inhibition of SIRT2 suppresses the phosphorylation of ERK, which is critical for the stabilization of c-MYC. Moreover, we found that Sirt2 deficiency attenuates the hepatic fibrosis induced by carbon tetrachloride (CCl4) and thioacetamide (TAA). Furthermore, we showed that SIRT2, p-ERK, and c-MYC proteins are all overexpressed in human hepatic fibrotic tissues. These data suggest a critical role for the SIRT2/ERK/c-MYC axis in promoting hepatic fibrogenesis. Inhibition of the SIRT2/ERK/c-MYC axis represents a novel strategy to prevent and to potentially treat liver fibrosis and cirrhosis.

PS-094-Selective activation of JAK-STATl-mediated apoptosis in hepatic stellate cells as a new therapeutic option for liver fibrosis: Role of rilpivirine

2019 ◽  
Vol 70 (1) ◽  
pp. e60-e61
Author(s):  
Alberto Martí-Rodrigo ◽  
Ángela B. Moragrega ◽  
Aleksandra Gruevska ◽  
Anabel Fernández-Iglesias ◽  
Jordi Gracia-Sancho ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Hepatic Stellate Cells ◽  
Therapeutic Option ◽  
Stellate Cells ◽  
Selective Activation

The role of S100A4 in liver fibrosis and the activation of hepatic stellate cells

2003 ◽  
Vol 124 (4) ◽  
pp. A717
Author(s):  
Chunqing Zhang ◽  
Lin Xu ◽  
Junmei Jiang ◽  
Chengyong Qin
Keyword(s):  
Liver Fibrosis ◽  
Hepatic Stellate Cells ◽  
Stellate Cells

scholarly journals Role of TGF-β signaling in differentiation of mesothelial cells to vitamin A-poor hepatic stellate cells in liver fibrosis

2016 ◽  
Vol 310 (4) ◽  
pp. G262-G272 ◽  
Author(s):  
Yuchang Li ◽  
Ingrid Lua ◽  
Samuel W. French ◽  
Kinji Asahina
Keyword(s):  
Liver Fibrosis ◽  
Vitamin A ◽  
Hepatic Stellate Cells ◽  
Transforming Growth Factor ◽  
Stellate Cells ◽  
Mesothelial Cells ◽  
Mesenchymal Transition ◽  
Duct Ligation ◽  
Liver Surface

Mesothelial cells (MCs) form a single layer of the mesothelium and cover the liver surface. A previous study demonstrated that, upon liver injury, MCs migrate inward from the liver surface and give rise to hepatic stellate cells (HSCs) in biliary fibrosis induced by bile duct ligation (BDL) or myofibroblasts in CCl4-induced fibrosis. The present study analyzed the role of transforming growth factor-β (TGF-β) signaling in mesothelial-mesenchymal transition (MMT) and the fate of MCs during liver fibrosis and its regression. Deletion of TGF-β type II receptor ( Tgfbr2) gene in cultured MCs suppressed TGF-β-mediated myofibroblastic conversion. Conditional deletion of Tgfbr2 gene in MCs reduced the differentiation of MCs to HSCs and myofibroblasts in the BDL and CCl4 models, respectively, indicating that the direct TGF-β signaling in MCs is responsible to MMT. After BDL and CCl4 treatment, MC-derived HSCs and myofibroblasts were distributed near the liver surface and the thickness of collagen was increased in Glisson's capsule beneath the liver surface. Fluorescence-activated cell sorting analysis revealed that MC-derived HSCs and myofibroblasts store little vitamin A lipids and have fibrogenic phenotype in the fibrotic livers. MCs contributed to 1.4 and 2.0% of activated HSCs in the BDL and CCl4 models, respectively. During regression of CCl4-induced fibrosis, 20% of MC-derived myofibroblasts survived in the liver and deactivated to vitamin A-poor HSCs. Our data indicate that MCs participate in capsular fibrosis by supplying vitamin A-poor HSCs during a process of liver fibrosis and regression.

scholarly journals CD8+ tissue-resident memory T cells promote liver fibrosis resolution by inducing apoptosis of hepatic stellate cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yuzo Koda ◽  
Toshiaki Teratani ◽  
Po-Sung Chu ◽  
Yuya Hagihara ◽  
Yohei Mikami ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Hepatic Stellate Cells ◽  
Molecular Mechanisms ◽  
Stellate Cells ◽  
Dependent Manner ◽  
Resolution Model ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome ◽  
Resident Memory T Cells

AbstractNon-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease that can progress to liver fibrosis. Recent clinical advance suggests a reversibility of liver fibrosis, but the cellular and molecular mechanisms underlying NASH resolution remain unclarified. Here, using a murine diet-induced NASH and the subsequent resolution model, we demonstrate direct roles of CD8+ tissue-resident memory CD8+ T (CD8+ Trm) cells in resolving liver fibrosis. Single-cell transcriptome analysis and FACS analysis revealed CD69+CD103−CD8+ Trm cell enrichment in NASH resolution livers. The reduction of liver CD8+ Trm cells, maintained by tissue IL-15, significantly delayed fibrosis resolution, while adoptive transfer of these cells protected mice from fibrosis progression. During resolution, CD8+ Trm cells attracted hepatic stellate cells (HSCs) in a CCR5-dependent manner, and predisposed activated HSCs to FasL-Fas-mediated apoptosis. Histological assessment of patients with NASH revealed CD69+CD8+ Trm abundance in fibrotic areas, further supporting their roles in humans. These results highlight the undefined role of liver CD8+ Trm in fibrosis resolution.

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