Modern pathogenetic concepts of liver fibrosis suggest stellate cells and TGF-beta as major players and therapeutic targets.
Modern pathogenetic concepts of liver fibrosis suggest stellate cells and TGF-beta as major players and therapeutic targets.
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DOI：
10.1111/j.1582-4934.2006.tb00292.x
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发表时间：
2006-01
影响因子：
5.3
通讯作者：
Weiskirchen R
中科院分区：
文献类型：
--
作者：
Gressner AM;Weiskirchen R
肝纤维化是一种瘢痕形成过程，与肝脏细胞外基质沉积增加和改变有关。在细胞和分子水平上，这一渐进过程主要表现为肝星状细胞的细胞活化和转化生长因子-β1及其下游细胞介质的异常活性。尽管细胞对这种细胞因子的反应是复杂的，但这种关键细胞因子在纤维化反应中的信号通路及其与其他信号级联的联系现在已经有了一些详细的了解。基于目前对纤维形成过程中多效性反应的理解，各种转化生长因子-β抑制剂被开发出来，目前正在作为肝损伤实验模型的潜在候选药物进行研究。虽然现在确定这些拮抗剂中的一种用于治疗人类肝纤维化还为时过早，但所获得的实验结果为在不久的将来开发一种有效的治疗方法提供了刺激。本文综述了肝纤维化的发病机制，转化生长因子-β及其信号通路在促进纤维化反应中的作用，以及目前许多研究关注的治疗方式，并已经进入临床研究。
Hepatic fibrosis is a scarring process that is associated with an increased and altered deposition of extracellular matrix in liver. At the cellular and molecular level, this progressive process is mainly characterized by cellular activation of hepatic stellate cells and aberrant activity of transforming growth factor-β1 and its downstream cellular mediators. Although the cellular responses to this cytokine are complex, the signalling pathways of this pivotal cytokine during the fibrogenic response and its connection to other signal cascades are now understood in some detail. Based on the current advances in understanding the pleiotropic reactions during fibrogenesis, various inhibitors of transforming growth factor-β were developed and are now being investigated as potential drug candidates in experimental models of hepatic injury. Although it is too early to favour one of these antagonists for the treatment of hepatic fibrogenesis in human, the experimental results obtained yet provide stimulatory impulses for the development of an effective treatment of choice in the not too distant future. The present review summarises the actual knowledge on the pathogenesis of hepatic fibrogenesis, the role of transforming growth factor-β and its signalling pathways in promoting the fibrogenic response, and the therapeutic modalities that are presently in the spotlight of many investigations and are already on the way to take the plunge into clinical studies.
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DOI：
10.1007/bf01675207
发表时间：
1986-06-01
期刊：
HISTOCHEMICAL JOURNAL
影响因子：
--
作者：
ATERMAN, K
通讯作者：
ATERMAN, K
影响因子：
5
作者：
Borkham-Kamphorst, E;Herrmann, J;Weiskirchen, R
通讯作者：
Weiskirchen, R
DOI：
10.1073/pnas.0409722102
发表时间：
2005-03-01
影响因子：
11.1
作者：
Campbell, JS;Hughes, SD;Fausto, N
通讯作者：
Fausto, N
影响因子：
2.4
作者：
Arias M;Sauer-Lehnen S;Treptau J;Janoschek N;Theuerkauf I;Buettner R;Gressner AM;Weiskirchen R
通讯作者：
Weiskirchen R
影响因子：
6.4
作者：
Bandapalli, OR;Geheeb, M;Brand, K
通讯作者：
Brand, K