Current perspectives on the role of autophagy in liver fibrosis
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摘要:
细胞自噬是细胞内的一种代谢过程,通过细胞内的膜结构包裹部分胞质和细胞内需降解的细胞器、蛋白质等形成自噬小体,然后与溶酶体融合降解其所包裹内容物,其降解产物氨基酸、游离脂肪酸等可供细胞物质能量循环,细胞自噬在肝脏疾病的发生发展中有重要的作用,最近研究表明,细胞自噬可以通过降解脂滴为肝星状细胞的活化提供能量从而促进肝纤维化的发生。
Abstract:Liver disease, especially liver fibrosis, remains a major health challenge in China.In order to develop effective preventive and therapeutic interventions of liver fibrosis, the related etiologies and key pathogenic mechanisms must be understood.Upon liver damage, the hepatic stellate cells (HSCs) are activated and secrete robust amounts of inflammatory cytokines and extracellular matrix proteins, leading to fibrosis.A recently recognized mediator of HSC activation is autophagy, a necessary metabolic process of protein cycling for energy production.More recently, however, a role for autophagy in HSC-mediated liver fibrosis has been suggested.This review summarizes the reported evidence of increased autophagy and HSC activation in fibrosis and discusses the potential role of autophage-degraded lipid droplets as energy sources for activating HSCs.In addition, the review briefly highlights the current research of autophagy and HSCs in relation to hepatitis virus infection, a major etiology of liver disease and fibrosis in China.By gaining a comprehensive and detailed understanding of the role of autophagy in liver disease, novel and improved therapies may be developed, targeting physiological pathways of the patient's liver or immune system or of an invading pathogen, such as hepatitis virus replication.
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Key words:
- autophagy /
- liver cirrhoisis /
- hepatocytes /
- astrocytes
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