Role of hepatic progenitor cells in nonalcoholic fatty liver disease development: cellular cross-talks and molecular networks.
Role of hepatic progenitor cells in nonalcoholic fatty liver disease development: cellular cross-talks and molecular networks.
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DOI：
10.3390/ijms141020112
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发表时间：
2013-10-09
影响因子：
5.6
通讯作者：
Gaudio E
中科院分区：
文献类型：
--
作者：
Carpino G;Renzi A;Onori P;Gaudio E
非酒精性脂肪性肝病（NAFLD）包括一系列疾病，从单纯性脂肪肝到非酒精性脂肪性肝炎（NASH），NASH可能进展为肝硬化和肝细胞癌。NASH与动脉粥样硬化进展和心血管风险独立相关。NASH发展的特征在于使肝损伤进展的驻留细胞和募集细胞之间的复杂相互作用。越来越多的共识是，NAFLD中肝细胞、肝星状细胞（HSC）和巨噬细胞之间的串扰在脂质稳态、胰岛素抵抗、危险识别、免疫耐受反应和纤维化的紊乱中起主要作用。此外，一些证据表明，肝干/祖细胞（HPC）激活是NAFLD中肝脏对氧化应激的适应性反应的一个组成部分。HPC激活决定了小管反应的出现。在NASH中，小管反应与进行性门静脉纤维化独立相关，这提高了门静脉周围纤维发生途径的可能性，该途径与HSC在3区中沉积的窦下胶原平行。最近的研究表明，脂肪因子作为一类循环因子，在HSC、HPC和肝巨噬细胞之间的相互作用中起着关键作用。本文就NASH进展和纤维化过程中细胞间的相互作用及其相关的分子网络作一综述。
Nonalcoholic fatty liver disease (NAFLD) includes a spectrum of diseases ranging from simple fatty liver to nonalcoholic steatohepatitis, (NASH) which may progress to cirrhosis and hepatocellular carcinoma. NASH has been independently correlated with atherosclerosis progression and cardiovascular risk. NASH development is characterized by intricate interactions between resident and recruited cells that enable liver damage progression. The increasing general agreement is that the cross-talk between hepatocytes, hepatic stellate cells (HSCs) and macrophages in NAFLD has a main role in the derangement of lipid homeostasis, insulin resistance, danger recognition, immune tolerance response and fibrogenesis. Moreover, several evidences have suggested that hepatic stem/progenitor cell (HPCs) activation is a component of the adaptive response of the liver to oxidative stress in NAFLD. HPC activation determines the appearance of a ductular reaction. In NASH, ductular reaction is independently correlated with progressive portal fibrosis raising the possibility of a periportal fibrogenetic pathway for fibrogenesis that is parallel to the deposition of subsinusoidal collagen in zone 3 by HSCs. Recent evidences indicated that adipokines, a class of circulating factors, have a key role in the cross-talk among HSCs, HPCs and liver macrophages. This review will be focused on cellular cross-talk and the relative molecular networks which are at the base of NASH progression and fibrosis.
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DOI：
10.1124/jpet.108.136721
发表时间：
2008-06-01
影响因子：
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作者：
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