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Mechanisms and Biomarkers of Apoptosis in Liver Disease and Fibrosis

机译:肝病和纤维化中细胞凋亡的机制和生物标志物

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Liver fibrosis and cirrhosis are a major cause of morbidity and mortality worldwide. Development of the fibrotic scar is an outcome of chronic liver diseases of varying aetiologies including alcoholic liver disease (ALD) nonalcoholic liver disease (NAFLD) including non-alcoholic steatohepatitis (NASH) viral hepatitis B and C (HBV, HCV). The critical step in the development of scar is activation of hepatic stellate cells (HSCs), which become the primary source of extracellular matrix. Aberrant apoptosis is a feature of chronic liver diseases and is associated with worsening stages of fibrosis. However, apoptosis is also the main mechanism promoting the resolution of fibrosis, and spontaneous or targeted apoptosis of HSC is associated with regression of fibrosis in animal models and patients with chronic liver disease. Given the importance of apoptosis in disease progression and resolution, there is much interest in precisely delineating the mechanisms involved and also developing biomarkers that accurately reflect the underlying pathogenesis. Here, we review the mechanisms driving apoptosis in development of liver disease and use of apoptosis -related biomarkers to aid in clinical diagnosis. Finally, we will also examine the recent literature regarding new insights into mechanisms involved in apoptosis of activated HSCs as possible method of fibrosis regression.
机译:肝纤维化和肝硬化是全世界发病率和死亡率的主要原因。纤维化疤痕的形成是各种病因的慢性肝脏疾病的结果,包括酒精性肝病(ALD),非酒精性肝病(NAFLD),包括非酒精性脂肪性肝炎(NASH)乙型和丙型病毒性肝炎(HBV,HCV)。疤痕形成的关键步骤是激活肝星状细胞(HSC),后者成为细胞外基质的主要来源。异常的细胞凋亡是慢性肝病的特征,并且与纤维化的恶化阶段有关。然而,凋亡也是促进纤维化消退的主要机制,并且在动物模型和患有慢性肝病的患者中,HSC的自发性或靶向性凋亡与纤维化的消退相关。考虑到细胞凋亡在疾病进展和解决中的重要性,人们对精确描述所涉及的机制以及开发能够准确反映潜在发病机制的生物标志物非常感兴趣。在这里,我们综述了在肝病发展过程中驱动细胞凋亡的机制以及与细胞凋亡相关的生物标记物在临床诊断中的帮助。最后,我们还将研究有关激活HSCs凋亡作为纤维化消退的可能机制的新见解的最新文献。

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