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Modern pathogenetic concepts of liver fibrosis suggest stellate cells and
TGF-beta as major players and therapeutic targets
#MMPMID16563223
Gressner AM
; Weiskirchen R
J Cell Mol Med
2006[Jan]; 10
(1
): 76-99
PMID16563223
show ga
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-beta1 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-beta 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-beta
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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