scholarly journals Autophagy: A Multifaceted Partner in Liver Fibrosis

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Ariane Mallat ◽  
Jasper Lodder ◽  
Fatima Teixeira-Clerc ◽  
Richard Moreau ◽  
Patrice Codogno ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Cell Activation ◽  
Stellate Cell ◽  
Parenchymal Cell ◽  
High Morbidity ◽  
Antifibrotic Therapy ◽  
End Stage ◽  
Matrix Accumulation ◽  
Parenchymal Cells ◽  
Apoptosis And Necrosis

Liver fibrosis is a common wound healing response to chronic liver injury of all causes, and its end-stage cirrhosis is responsible for high morbidity and mortality worldwide. Fibrosis results from prolonged parenchymal cell apoptosis and necrosis associated with an inflammatory reaction that leads to recruitment of immune cells, activation and accumulation of fibrogenic cells, and extracellular matrix accumulation. The fibrogenic process is driven by hepatic myofibroblasts, that mainly derive from hepatic stellate cells undergoing a transdifferentiation from a quiescent, lipid-rich into a fibrogenic myofibroblastic phenotype, in response to paracrine/autocrine signals produced by neighbouring inflammatory and parenchymal cells. Autophagy is an important regulator of liver homeostasis under physiological and pathological conditions. This review focuses on recent findings showing that autophagy is a novel, but complex, regulatory pathway in liver fibrosis, with profibrogenic effects relying on its direct contribution to the process of hepatic stellate cell activation, but with antifibrogenic properties via indirect hepatoprotective and anti-inflammatory properties. Therefore, cell-specific delivery of drugs that exploit autophagic pathways is a prerequisite to further consider autophagy as a potential target for antifibrotic therapy.

scholarly journals Novel Therapeutic Targets in Liver Fibrosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Jinhang Zhang ◽  
Qinhui Liu ◽  
Jinhan He ◽  
Yanping Li
Keyword(s):  
Liver Fibrosis ◽  
Cell Activation ◽  
Stellate Cell ◽  
Cell Metabolism ◽  
Therapeutic Targets ◽  
Inflammatory Cells ◽  
Nonparenchymal Cells ◽  
End Stage ◽  
New Treatments ◽  
Novel Therapeutic

Liver fibrosis is end-stage liver disease that can be rescued. If irritation continues due to viral infection, schistosomiasis and alcoholism, liver fibrosis can progress to liver cirrhosis and even cancer. The US Food and Drug Administration has not approved any drugs that act directly against liver fibrosis. The only treatments currently available are drugs that eliminate pathogenic factors, which show poor efficacy; and liver transplantation, which is expensive. This highlights the importance of clarifying the mechanism of liver fibrosis and searching for new treatments against it. This review summarizes how parenchymal, nonparenchymal cells, inflammatory cells and various processes (liver fibrosis, hepatic stellate cell activation, cell death and proliferation, deposition of extracellular matrix, cell metabolism, inflammation and epigenetics) contribute to liver fibrosis. We highlight discoveries of novel therapeutic targets, which may provide new insights into potential treatments for liver fibrosis.

scholarly journals Diagnostic value of serum leptin as a tumor marker in hepatocellular carcinoma

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
K Abdelwahab ◽  
M Abdelmaaboud ◽  
M Magdy ◽  
M A Abdelhalim
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Fibrosis ◽  
Tumor Marker ◽  
Cell Activation ◽  
Stellate Cell ◽  
Peptide Hormone ◽  
Abdominal Ultrasound ◽  
Diagnostic Value ◽  
Serum Leptin ◽  
End Stage

Abstract Background Leptin is a peptide hormone produced by adipocytes, acts on the energy balance of reproduction and immunomodulation, and this action is linked to the pathogenesis of many diseases. High levels of this hormone increase hepatic response to various stimuli of liver fibrosis. Leptin acts to mediate hepatic stellate cell activation and liver fibrosis throughout indirect effects on Kupffer cells The aim The aim is to evaluate diagnostic value of serum leptin as a tumor marker in hepatocellular carcinoma (HCC). Methods 90 Egyptian subjects were conducted to this study after their written informed consent. They divided into 4 groups (30 patients with untreated HCC, 30 patients with treated HCC, 15 patients with end stage chronic liver disease without HCC and 15 healthy controls). They subjected to full history, examination, laboratory investigation and abdominal ultrasound. Serum leptin assessment is done using ELISA method. Results Leptin level is increased in all patients groups compared to control ((med. 40 IQR 37-50, med. 8 IQR 3-20, med. 2 IQR 1-4 VS med.1 IQR 1-1 ng/ml respectively) also it was higher in untreated HCC and treated HCC patients than patients without HCC. (med. 40 IQR 37-50, med. 8 IQR 3-20 VS med. 2 IQR 1-4) . Furthermore, leptin level is higher in untreated HCC than treated HCC(med. 40 IQR 37-50 VS med. 8 IQR 3-20) Leptin positively correlated with HCC Conclusion Leptin level in HCC either untreated or treated patients and in end stage CLD patients is higher than healthy .Also, it’s higher in HCC patients either untreated or treated than cirrhotic patients without HCC . Furthermore, leptin level is higher in un treated HCC than treated HCC patients.

scholarly journals Active Compounds Derived from Fuzheng Huayu Formula Protect Hepatic Parenchymal Cells from Apoptosis Based on Network Pharmacology and Transcriptomic Analysis

Molecules ◽  
2019 ◽  
Vol 24 (2) ◽  
pp. 338 ◽  
Author(s):  
Rong Wu ◽  
Shu Dong ◽  
Fei-Fei Cai ◽  
Xiao-Le Chen ◽  
Meng-Die Yang ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Stellate Cell ◽  
Parenchymal Cell ◽  
Transcriptomic Analysis ◽  
Tanshinone Iia ◽  
Network Pharmacology ◽  
Active Compounds ◽  
Parenchymal Cells

Fuzheng huayu formula (FZHY), an antifibrotic traditional Chinese medicine, is frequently used for the treatment of liver fibrosis. In this study, network analysis, transcriptomic analysis, assays of cell apoptosis, viability and protein expression were used for investigating the effects and mechanisms of compounds derived from FZHY on hepatic parenchymal cell (HPC) protection and hepatic stellate cell activation. Network pharmacology analysis found that 6 major compounds and 39 potential targets were important network nodes. Our analysis predicted that the active compounds of FZHY, including hederagenin, luteolin and tanshinone IIA inhibited cell apoptosis (p < 0.05), increased PI3K expression and reduced cleaved caspase 3 expression and the Bax/Bcl-w ratio (p < 0.05) in L02 cells that had apoptosis induced by TNF-α. Few significant changes caused by FZHY, hederagenin, luteolin and tanshinone IIA were observed in hepatic stellate Lx2 cells upon TGF-β1 induction. These data suggest that FZHY is active against liver fibrosis, protects hepatic parenchymal cells from apoptosis, and recovers liver function, possibly through the effects of its active compounds hederagenin, luteolin and tanshinone IIA and is involved in the inhibition of apoptosis in HPCs, possibly through regulating the PI3K, ERK, cleaved caspase 3 and Bax/Bcl-w levels.

scholarly journals Induction of tropomyosin during hepatic stellate cell activation and the progression of liver fibrosis

2008 ◽  
Vol 3 (2) ◽  
pp. 378-383 ◽  
Author(s):  
Kohji Otogawa ◽  
Tomohiro Ogawa ◽  
Ryoko Shiga ◽  
Kazuo Ikeda ◽  
Norifumi Kawada
Keyword(s):  
Liver Fibrosis ◽  
Hepatic Stellate Cell ◽  
Cell Activation ◽  
Stellate Cell ◽  
Hepatic Stellate Cell Activation

scholarly journals The mechanism of increased intestinal palmitic acid absorption and its impact on hepatic stellate cell activation in nonalcoholic steatohepatitis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Masakazu Hanayama ◽  
Yasunori Yamamoto ◽  
Hiroki Utsunomiya ◽  
Osamu Yoshida ◽  
Shuang Liu ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Portal Vein ◽  
Palmitic Acid ◽  
Intestinal Absorption ◽  
Nonalcoholic Steatohepatitis ◽  
Cell Activation ◽  
Stellate Cell ◽  
Mrna Levels ◽  
Nonalcoholic Fatty Liver ◽  
Chylomicron Formation

AbstractDietary palmitic acid (PA) promotes liver fibrosis in patients with nonalcoholic steatohepatitis (NASH). Herein, we clarified the intestinal absorption kinetics of dietary PA and effect of trans-portal PA on the activation of hepatic stellate cells (HSCs) involved in liver fibrosis in NASH. Blood PA levels after meals were significantly increased in patients with NASH compared to those in the control. Expression of genes associated with fat absorption and chylomicron formation, such as CD36 and MTP, was significantly increased in the intestine of NASH model rats compared with that in the controls. Plasma levels of glucagon-like peptide-2, involved in the upregulation of CD36 expression, were elevated in NASH rats compared with those in the controls. Furthermore, portal PA levels after meals in NASH rats were significantly higher than those in control and nonalcoholic fatty liver rats. Moreover, PA injection into the portal vein to the liver in control rats increased the mRNA levels associated with the activation of HSCs. Increased intestinal absorption of diet-derived PA was observed in NASH. Thus, the rapid increase in PA levels via the portal vein to the liver may activate HSCs and affect the development of liver fibrosis in NASH.

scholarly journals Dominant-negative soluble PDGF-β receptor inhibits hepatic stellate cell activation and attenuates liver fibrosis

2004 ◽  
Vol 84 (6) ◽  
pp. 766-777 ◽  
Author(s):  
Erawan Borkham-Kamphorst ◽  
Jens Herrmann ◽  
Doris Stoll ◽  
Jens Treptau ◽  
Axel M Gressner ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Hepatic Stellate Cell ◽  
Cell Activation ◽  
Stellate Cell ◽  
Dominant Negative ◽  
Hepatic Stellate Cell Activation ◽  
Β Receptor
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