摘要
Hepatic fibrosis is a wound healing response, involving pathways of inflammation and fibrogenesis. In response to various insults, such as alcohol, ischemia, viral agents, and medications or hepatotoxins, hepatocyte damage will cause the release of cytokines and other soluble factors by Kupffer cells and other cell types in the liver. These factors lead to activation of hepatic stellate cells, which synthesize large amounts of extracellular matrix components. With chronic injury and fibrosis, liver architecture and metabolism are disrupted, eventually manifesting as cirrhosis and its complications. In addition to eliminating etiology, such as antiviral therapy and pharmacological intervention, it is encouraging that novel strategies are being developed to directly address hepatic injury and fibrosis at the subcellular and molecular levels. With improvement in understanding these mechanisms and pathways, key steps in injury, signaling, activation, and gene expression are being targeted by molecular modalities and other molecular or gene therapy approaches. This article intends to provide an update in terms of the current status of molecular therapy for hepatic injury and fibrosis and how far we are from clinical utilization of these new therapeutic modalities.
肝的纤维变性是弯屈的愈合的回答，包含发炎和纤维发生的小径。响应各种各样的侮辱，例如酒精，局部缺血，病毒的代理人，和药或肝毒素， hepatocyte 损坏将在肝由 Kupffer 房间和另外的房间类型引起 cytokines 和另外的可溶的因素的版本。这些因素导致肝的星形细胞的激活，它综合大量细胞外的矩阵部件。与长期的损害和纤维变性，肝建筑学和新陈代谢被破坏，最后作为肝硬化和它的复杂并发症表明。除了消除病原学，例如抗病毒的治疗和药理学干预，新奇策略正在被开发直接在细胞的潜水艇和分子的层次探讨肝的损害和纤维变性，这令人鼓舞。与在理解这些机制和小径的改进，在损害给步调音，发信号，激活，和基因表示被分子的形式和分子的其它或基因治疗途径正在指向。这篇文章打算为肝的损害和纤维变性以分子的治疗的当前的地位提供更改并且我们多远从这些新治疗学的形式的临床的利用。
基金
Supported by NIH grant(DK069939)
the Liver Scholar Award by the American Liver Foundation to J.W.
