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Proteoglycan and ADAMTS expression during fibrogenic remodeling in the liver
Author(s) -
Maurice Sean B,
Crick Cody,
Kim WanCheol,
Law Christine,
Kim SangEun,
Winwood Paul J
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.877.3
Subject(s) - versican , extracellular matrix , adamts , proteoglycan , matrix metalloproteinase , fibrosis , microbiology and biotechnology , hepatic stellate cell , pathology , chemistry , biology , metalloproteinase , medicine , thrombospondin , biochemistry
Liver fibrosis and end stage cirrhosis are leading causes of morbidity and mortality worldwide. Changes in the structure and composition of the proteoglycan rich extracellular matrix (ECM) are known to play a role in these processes, though these changes are incompletely understood and characterized. An increased understanding of these events may one day allow early recognition and targeted therapy, leading to the reversibility of liver fibrosis as a future clinical outcome. In other tissues, proteoglycans including versican are key components of fibrotic ECM that modulates cellular functions. The ADAMTS enzymes are now known to cleave versican and other proteoglycans in a manner previously ascribed to the MMPs. This work focuses on the role of the hepatic stellate cell in synthesizing a proteoglycan rich fibroproliferative ECM in vitro and in vivo. We have investigated several candidate proteoglycans, including versican, along with several candidate ADAMTS enzymes, in two models of liver fibrosis. Using qPCR and confocal microscopy, we report a more thorough expression profile for these important ECM constituents than has previously been described. These findings underscore the need to better characterize the fibroproliferative liver ECM. Grant Funding Source : Northern Medical Program