Cellular and molecular mechanisms in the pathogenesis of liver fibrosis: An update
Cellular and molecular mechanisms in the pathogenesis of liver fibrosis: An update
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DOI：
10.3748/wjg.v20.i23.7260
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发表时间：
2014-06-21
影响因子：
4.3
通讯作者：
Elpek, Gulsum Ozlem
中科院分区：
文献类型：
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作者：
Elpek, Gulsum Ozlem
最近有相当大的进展，以更好地了解复杂的细胞和分子网络的基础上肝纤维化。最近的数据表明，纤维化过程的终止和纤维溶解途径缺陷的恢复可能会逆转晚期纤维化甚至肝硬化。因此，人们一直在努力更好地阐明参与肝纤维化的细胞和分子机制。肝星状细胞（HSC）的活化仍然是纤维化的中心事件，由其他来源的基质产生细胞补充，包括门静脉成纤维细胞、纤维细胞和骨髓源性肌成纤维细胞。这些细胞聚集在一个复杂的相互作用与邻近的细胞，以挑起疤痕，以应对持续性损伤。定义不同细胞类型之间的相互作用，揭示细胞因子对这些细胞的影响，并表征控制活化HSC中基因表达的调控机制，将有助于发现新的治疗靶点。此外，与不同病因相关的不同途径的表征有助于开发疾病特异性疗法。本文概述了肝纤维化的细胞和分子机制的最新进展，可能会转化为未来的治疗。本文还讨论了与酒精性肝病、非酒精性脂肪性肝病和病毒性肝炎相关的肝纤维化的发病机制，以强调肝纤维化的各种机制。(C)2014百世登出版集团股份有限公司All rights reserved.
There have been considerable recent advances towards a better understanding of the complex cellular and molecular network underlying liver fibrogenesis. Recent data indicate that the termination of fibrogenic processes and the restoration of deficient fibrolytic pathways may allow the reversal of advanced fibrosis and even cirrhosis. Therefore, efforts have been made to better clarify the cellular and molecular mechanisms that are involved in liver fibrosis. Activation of hepatic stellate cells (HSCs) remains a central event in fibrosis, complemented by other sources of matrix-producing cells, including portal fibroblasts, fibrocytes and bone marrow-derived myofibroblasts. These cells converge in a complex interaction with neighboring cells to provoke scarring in response to persistent injury. Defining the interaction of different cell types, revealing the effects of cytokines on these cells and characterizing the regulatory mechanisms that control gene expression in activated HSCs will enable the discovery of new therapeutic targets. Moreover, the characterization of different pathways associated with different etiologies aid in the development of disease-specific therapies. This article outlines recent advances regarding the cellular and molecular mechanisms involved in liver fibrosis that may be translated into future therapies. The pathogenesis of liver fibrosis associated with alcoholic liver disease, non-alcoholic fatty liver disease and viral hepatitis are also discussed to emphasize the various mechanisms involved in liver fibrosis. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.