RGD Reference Report - Connective tissue growth factor with a novel fibronectin binding site promotes cell adhesion and migration during rat oval cell activation. - Rat Genome Database

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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.
RGD ID: 2314623
Pubmed: PMID:18167060   (View Abstract at PubMed)
PMCID: PMC3130595   (View Article at PubMed Central)
DOI: DOI:10.1002/hep.22079   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
myocardial infarction  ISOCcn2 (Rattus norvegicus)2314623; 2314623mRNA:increased expression:left ventricle (rat)RGD 
myocardial infarction  IEP 2314623mRNA:increased expression:left ventricle (rat)RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of cell migration  IMP 2314623 RGD 
positive regulation of cell migration  IMP 2314623oval hepatic stem cellsRGD 
positive regulation of cell-substrate adhesion  IMP 2314623; 2314623 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
fibronectin binding  IDA 2314623 RGD 
integrin binding  IPIItgb1 (Rattus norvegicus)2314623 RGD 
integrin binding  IPIItga5 (Rattus norvegicus)2314623 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccn2  (cellular communication network factor 2)
Itga5  (integrin subunit alpha 5)
Itgb1  (integrin subunit beta 1)

Genes (Mus musculus)
Ccn2  (cellular communication network factor 2)

Genes (Homo sapiens)
CCN2  (cellular communication network factor 2)


Additional Information