RGD Reference Report - Loss of Gab1 adaptor protein in hepatocytes aggravates experimental liver fibrosis in mice. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources
Advanced Search (OLGA)

Loss of Gab1 adaptor protein in hepatocytes aggravates experimental liver fibrosis in mice.

Authors: Kizu, Takashi  Yoshida, Yuichi  Furuta, Kunimaro  Ogura, Satoshi  Egawa, Mayumi  Chatani, Norihiro  Hamano, Mina  Takemura, Takayo  Ezaki, Hisao  Kamada, Yoshihiro  Nishida, Keigo  Nakaoka, Yoshikazu  Kiso, Shinichi  Takehara, Tetsuo 
Citation: Kizu T, etal., Am J Physiol Gastrointest Liver Physiol. 2015 Apr 1;308(7):G613-24. doi: 10.1152/ajpgi.00289.2014. Epub 2015 Jan 23.
RGD ID: 14995329
Pubmed: PMID:25617348   (View Abstract at PubMed)
DOI: DOI:10.1152/ajpgi.00289.2014   (Journal Full-text)

Grb2-associated binder 1 (Gab1) adaptor protein amplifies signals downstream of a broad range of growth factors/receptor tyrosine kinases. Although these signals are implicated in liver fibrogenesis, the role of Gab1 remains unclear. To elucidate the role of Gab1, liver fibrosis was examined in hepatocyte-specific Gab1-conditional knockout (Gab1CKO) mice upon bile duct ligation (BDL). Gab1CKO mice developed exacerbated liver fibrosis with activation of hepatic myofibroblasts after BDL compared with control mice. The antifibrotic role of hepatocyte Gab1 was further confirmed by another well-established mouse model of liver fibrosis using chronic injections of carbon tetrachloride. After BDL, Gab1CKO mice also displayed exacerbated liver injury, decreased hepatocyte proliferation, and enhanced liver inflammation. Furthermore, cDNA microarray analysis was used to investigate the potential molecular mechanisms of the Gab1-mediated signal in liver fibrosis, and the fibrosis-promoting factor chemokine (C-C motif) ligand 5 (Ccl5) was identified as upregulated in the livers of Gab1CKO mice following BDL. Interestingly, in vitro studies using primary hepatocytes isolated from control and Gab1CKO mice revealed that the loss of Gab1 resulted in increased hepatocyte CCL5 synthesis upon lipopolysaccharide stimulation. Finally, pharmacological antagonism of CCL5 reduced BDL-induced liver fibrosis in Gab1CKO mice. In conclusion, our results demonstrate that hepatocyte Gab1 is required for liver fibrosis and that hepatocyte CCL5 could be an important contributor to this process. Thus, we present a novel antifibrotic function of hepatocyte Gab1 in liver fibrogenesis.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CCL5HumanExperimental Liver Cirrhosis disease_progressionISOCcl5 (Mus musculus) RGD 
Ccl5RatExperimental Liver Cirrhosis disease_progressionISOCcl5 (Mus musculus) RGD 
Ccl5MouseExperimental Liver Cirrhosis disease_progressionIGIGab1 (Mus musculus) RGD 
GAB1HumanExperimental Liver Cirrhosis  ISOGab1 (Mus musculus)protein:increased tyrosine phosphorylation: :RGD 
Gab1RatExperimental Liver Cirrhosis  ISOGab1 (Mus musculus)protein:increased tyrosine phosphorylation: :RGD 
Gab1MouseExperimental Liver Cirrhosis  IDA protein:increased tyrosine phosphorylation: :RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccl5  (C-C motif chemokine ligand 5)
Gab1  (GRB2-associated binding protein 1)

Genes (Mus musculus)
Ccl5  (C-C motif chemokine ligand 5)
Gab1  (growth factor receptor bound protein 2-associated protein 1)

Genes (Homo sapiens)
CCL5  (C-C motif chemokine ligand 5)
GAB1  (GRB2 associated binding protein 1)


Additional Information