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Connective tissue growth factor with a novel fibronectin binding site promotes cell adhesion and migration during rat oval cell activation
Author(s) -
Pi Liya,
Ding Xiaodong,
Jorgensen Marda,
Pan JenJung,
Oh SehHoon,
Pintilie Dana,
Brown Alicia,
Song WenYuan,
Petersen Bryon E.
Publication year - 2008
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.22079
Subject(s) - ctgf , fibronectin , microbiology and biotechnology , extracellular matrix , integrin , growth factor , liver regeneration , connective tissue , hepatic stellate cell , biology , cell adhesion , chemistry , regeneration (biology) , cell , biochemistry , endocrinology , receptor , genetics
Oval cell activation, as part of the regenerative process after liver injury, involves considerable cell‐matrix interaction. The matricellular protein, connective tissue growth factor (CTGF), has been shown to be critical for oval cell activation during liver regeneration following N‐2‐acetylaminofluorene/partial hepatectomy. To understand the mode of action of CTGF during this process, N‐terminal CTGF was used as bait to screen a yeast two‐hybrid complementary DNA library specific for regenerating livers with massive oval cell presence. Fibronectin (FN), a prominent component of hepatic extracellular matrix (ECM), was found to specifically bind to a new site on CTGF. In addition to module IV, this study showed that module I of CTGF was sufficient for binding to FN in both solid‐phase in vitro binding assays and immunoprecipitation. Immunofluorescent staining revealed a dynamic ECM remodeling characterized by an FN‐concentrated provisional matrix during oval cell–aided liver regeneration. Abundant CTGF protein was colocalized with FN in the provisional matrix. When expressed as recombinant proteins and immobilized on plastic surfaces, modules I and IV of CTGF were selectively adhesive to thymus cell antigen 1–positive (Thy1 + ) oval cells, stellate cells, and sinusoidal endothelial cells but not to hepatocytes. The adhesion of these two modules on Thy1 + oval cells required heparan sulfate proteoglycan and integrin α 5 β 1 . Recombinant CTGF promoted an integrin α 5 β 1 –dependent migration but not proliferation on Thy1 + oval cells. Conclusion: Modules I and IV enabled the linkage of CTGF to FN and activated hepatic cells. Through these bindings, CTGF on the FN‐concentrated provisional matrix promoted cell adhesion and migration, thereby facilitating oval cell activation. (H EPATOLOGY 2007.)