Effect of hepatic stellate cells in liver fibrosis regression
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Liver fibrosis is considered as a serious disease,which can lead to portal hypertension,liver cirrhosis and liver failure.It has been well established that the activation of hepatic stellate cells plays a vital role in the hepatic fibrosis.Inhibiting hepatic stellate cells activation and accelerating clearance of hepatic stellate cells are promising strategies against liver fibrosis.In this assay,apoptosis,senescence and the clearance of the activated hepatic stellate cells will be reviewed,which aims to demonstrate the effect of hepatic stellate cells and its mechanism in hepatic fibrosis regression.Keywords:
Hepatic stellate cell
Hepatic fibrosis
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Hepatic stellate cell
Hepatic fibrosis
Liver cytology
Liver cell
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In response to liver injury, hepatic stellate cells activate and acquire proliferative and contractile features. The regression of liver fibrosis appears to involve the clearance of activated hepatic stellate cells, either by apoptosis or by reversion toward a quiescent-like state, a process called deactivation. Thus, deactivation of active hepatic stellate cells has emerged as a novel and promising therapeutic approach for liver fibrosis. However, our knowledge of the master regulators involved in the deactivation and/or activation of fibrotic hepatic stellate cells is still limited. The transcription factor GATA4 has been previously shown to play an important role in embryonic hepatic stellate cell quiescence. In this work, we show that lack of GATA4 in adult mice caused hepatic stellate cell activation and, consequently, liver fibrosis. During regression of liver fibrosis, Gata4 was reexpressed in deactivated hepatic stellate cells. Overexpression of Gata4 in hepatic stellate cells promoted liver fibrosis regression in CCl4-treated mice. GATA4 induced changes in the expression of fibrogenic and antifibrogenic genes, promoting hepatic stellate cell deactivation. Finally, we show that GATA4 directly repressed EPAS1 transcription in hepatic stellate cells and that stabilization of the HIF2α protein in hepatic stellate cells leads to liver fibrosis.
Hepatic stellate cell
Hepatic fibrosis
GATA4
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肝纤维化是肝脏对慢性损伤的一种修复反应,其特征表现为细胞外基质的过度沉积.肝星状细胞的激活是肝纤维化的关键环节.此文概述了细胞因子、细胞外基质、氧化应激和核转录因子对肝星状细胞激活的作用。
Hepatic stellate cell
Hepatic fibrosis
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肝纤维化是指各种致病因素所致的肝脏内纤维结缔组织增生,其特点是大量细胞外基质(extracellular matrix,ECM)在窦周间隙沉积.而肝星状细胞(hepatic stellate cells,HSC)是肝纤维化细胞外基质的主要来源细胞,在肝纤维化的形成中起关键作用,HSC活化已成为肝纤维化基础研究的热点。
Hepatic stellate cell
Liver cytology
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Activation of stellate cells as a target for the treatment of liver fibrosisIn his thesis, Zhang introduces the crucial role of hepatic stellate cell activation in the development of liver fibrosis. Activated liver stellate cells are the main precursors of myofibroblasts. Therapy targeting hepatic stellate cells can prevent or reverse liver fibrosis.The aging ("senescence") of hepatic stellate cells is interpreted as a mechanism that protects against the progression of liver fibrosis. The biomarkers, signaling pathways and likely effects of hepatic stellate cell senescence are explained. Zhang proposes that the biomarkers P21 (cell cycle arrest), senescence-associated β-galactosidase (lysosomal galactosidase), and interleukin-6 (senescence-associated secretory phenotype) can be used to identify senescent hepatic stellate cells. Although the senescence of liver stellate cells has not yet been fully elucidated, therapy-induced senescence of hepatic stellate cells, followed by senolytics, may be an optimal strategy for combating liver fibrosis.Esculetin, a coumarin derivative, has also been shown to cause the senescence of hepatic stellate cells. It appears that in senescent hepatic stellate cells, collagen production and cell proliferation are reduced. In addition, senescent hepatic stellate cells develop resistance to a return to active proliferation.
Hepatic stellate cell
Senescence
Hepatic fibrosis
Liver cytology
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Hepatic stellate cell
Hepatic fibrosis
Liver cytology
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Introduction Hepatic stellate cells (HSCs), in response to various inflammatory stimuli, undergo phenotypic changes from non-proliferating to proliferating cells that express alpha-smooth-muscle actin (α-SMA). Previous studies suggest that the estrogen presents an antifibrogenic action through inhibiting the myofibroblastic transformation of HSCs. The aim of this study is twofold: first, to understand the impact of early HSC activation on the fibrotic evolution of liver allografts; second, to find out the effect of estrogen and gender on this process. Materials and Methods Liver allograft biopsies of 71 (M/F: 49/22) cases that taken during first 4 months included in the study. All biopsies scored for liver fibrosis(LF) and immunostained with the estrogen receptor (ER), α-SMA, and TGF-β. Activated HSCs determined by the expression of α-SMA. Only 50 patients had follow-up biopsies taken within 18 months, and all 50 biopsies were scored for LF. Results Evaluation of initial first biopsy showed that only 35 of 71 patients had LF and almost all had fibrosis score (FS) lower than 2. Among 50 patients who had follow-up biopsies, 33 had developed variable scores of LF after initial biopsy. Of 71 patients 15 (M/F: 13/2) had no ER expression while 56 (M/F: 36/20) showed ER expression. Women showed higher degrees of ER expression compared to men (p<.001). The degree of LF both in initial and follow-up biopsies found to increase with decreasing ER expression (p<.01) and increasing degree of α-SMA and TGF-β expression (p<.001).ER expression in liver showed a significant negative correlation with α-SMA and TGF-β expression (p=.001).Also, the degree of the α-SMA and TGF-β expression found higher in males compared to females (p<.05). During 18 months the development of LF found higher in males and patients with low ER expression (p<.05). Patients with high expression of ER and women tend to develop a lower incidence of cirrhosis (p=.001), while men and patients with high expression of α-SMA and TGF-β developed a high frequency of cirrhosis(p<.01).Overall 5- and 10-year survival was 58% and 42% for negative and low ER expression while it was 82,5% and 80% for high ER expression (p=0.001). In multivariate logistic regression analyses, ER expression continued to be an independent predicting factor of liver fibrosis in patients (OR: 0.05; 95% CI: 0.01-0.248; P<.001). Conclusion Early activation of HSCs is a critical sign of the progressive fibrosis, and an increased number of HSCs represent an unfavorable event related to cirrhotic evolution. We suggested that lower progression of fibrosis in women may be due to the antifibrogenic action of estrogen which was confirmed by our results that ER expression in the liver has a negative correlation with HSCs and TGF-β expression. Consequently female and patients with high levels of estrogen have a better prognosis because of the antifibrotic action of estrogen.
Hepatic stellate cell
Hepatic fibrosis
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Hepatic stellate cell
Hepatic fibrosis
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Hepatic stellate cell
Hepatic fibrosis
Chronic hepatic
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Hepatic stellate cell
Primary (astronomy)
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