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- Title
Matrix Remodeling in Liver Fibrosis.
- Authors
Wan Kim; Crick, Cody; Sang-Eun Kim; Law, Christine; Maurice, Sean; Winwood, Paul John
- Abstract
The liver responds to injury in the same way most other tissues in the body do, by going through the processes of inflammation, tissue remodeling and wound healing. Recent evidence indicates that these processes are orchestrated by hepatic stellate cells (HSCs) which normally reside in the space of Dissé. Once HSCs are activated, they show similar characteristics to fibroblasts in other connective tissues as they begin to proliferate, reorganize cytoskeletal elements, and synthesize ECM components, particularly fibrillar collagens and proteoglycans (Moreira, 2007). Animal models have shown that once the damaging insult has been removed the liver restores itself to its original structure and function. However, in chronic liver fibrosis, it is thought that the altered structure of liver parenchyma and stoma is irreversible due to an ongoing insult resulting in molecular changes in its extracellular matrix (ECM). It is currently unknown what molecular changes direct the progression to chronic liver fibrosis versus structural restoration. One hypothesis that is being tested is that the increase in the levels of proteoglycans (PGs) and changes in the expression of ADAMTS enzymes are crucial in initiating HSC activation and influencing them to promote chronic fibrosis during persistent liver damage. In other tissues, PGs including versican are key components of fibrotic matrix that modulate cellular functions. The ADAMTS enzymes are now known to cleave versican and other proteoglycans in a manner previously ascribed to the matrix metalloproteinases. Hence, using activated hepatic stellate cells cultured in vitro and using mouse model of reversible liver fibrosis, we are investigating changes in the expression of versican and other candidate ECM proteoglycans as well as ADAMTS enzymes. Preliminary histological sections show that the liver fibrosis is reversible in our mouse model. Analysis of mRNA and protein expression levels of ECM proteins and ADAMTS enzymes are still on going in both our mouse model and in cultured HSCs in vitro.
- Subjects
FIBROSIS; LIVER diseases; INFLAMMATION; TISSUE remodeling; LIVER function tests
- Publication
UBC Medical Journal, 2011, Vol 2, Issue 2, p41
- ISSN
1920-7425
- Publication type
Abstract