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Connective tissue growth factor with a novel fibronectin binding site promotes cell adhesion and migration during rat oval cell activation.

Authors: Pi, L  Ding, X  Jorgensen, M  Pan, JJ  Oh, SH  Pintilie, D  Brown, A  Song, WY  Petersen, BE 
Citation: Pi L, etal., Hepatology. 2008 Mar;47(3):996-1004.
Pubmed: (View Article at PubMed) PMID:18167060
DOI: Full-text: DOI:10.1002/hep.22079

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 alpha(5)beta(1). Recombinant CTGF promoted an integrin alpha(5)beta(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.

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CRRD Object Information
CRRD ID: 2314623
Created: 2009-11-20
Species: All species
Last Modified: 2009-11-20
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.