Journal
TOXICOLOGY
Volume 254, Issue 3, Pages 120-129Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2008.06.013
Keywords
Hepatic fibrosis; Cirrhosis; Stellate cell; Extracellular matrix; Anti-fibrotic
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Funding
- NIDDK NIH HHS [DK56621, DK37340] Funding Source: Medline
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The study of hepatic fibrosis, or scarring in response to chronic liver injury, has witnessed tremendous progress in the past two decades. Clarification of the cellular sources of scar, and emergence of hepatic stellate cells not only as a fibrogenic cell type, but also as a critical immunomodulatory and homeostatic regulator are among the most salient advances. Activation of hepatic stellate cells remains a central event in fibrosis, complemented by evidence of additional sources of matrix-producing cells including bone marrow, portal fibroblasts, and epithelial-mesenchymal transition from both hepatocytes and cholangiocytes. A growing range of cytokines and their receptors and inflammatory cell subsets have further expanded our knowledge about this dynamic process. Collectively, these findings have laid the foundation for continued elucidation of underlying mechanisms, and more importantly for the implementation of rationally based approaches to limit fibrosis, accelerate repair and enhance liver regeneration in patients with chronic liver disease. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
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