RGD Reference Report - The role of AdipoR1 and AdipoR2 in liver fibrosis. - Rat Genome Database

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The role of AdipoR1 and AdipoR2 in liver fibrosis.

Authors: Alzahrani, Badr  Iseli, Tristan  Ramezani-Moghadam, Mehdi  Ho, Vikki  Wankell, Miriam  Sun, Eun Jin  Qiao, Liang  George, Jacob  Hebbard, Lionel W 
Citation: Alzahrani B, etal., Biochim Biophys Acta Mol Basis Dis. 2018 Mar;1864(3):700-708. doi: 10.1016/j.bbadis.2017.12.012. Epub 2017 Dec 10.
RGD ID: 24922203
Pubmed: PMID:29237572   (View Abstract at PubMed)
DOI: DOI:10.1016/j.bbadis.2017.12.012   (Journal Full-text)

Activation of the adiponectin (APN) signaling axis retards liver fibrosis. However, understanding of the role of AdipoR1 and AdipoR2 in mediating this response is still rudimentary. Here, we sought to elucidate the APN receptor responsible for limiting liver fibrosis by employing AdipoR1 and AdipoR2 knock-out mice in the carbon tetrachloride (CCl4) model of liver fibrosis. In addition, we knocked down receptor function in primary hepatic stellate cells (HSCs) in vitro. Following the development of fibrosis, AdipoR1 and AdipoR2 KO mice had no quantitative difference in fibrosis by Sirius red staining. However, AdipoR2 KO mice had an enhanced fibrotic signature with increased Col1-α1, TGFß-1, TIMP-1, IL-10, MMP-2 and MMP-9. Knockdown of AdipoR1 or AdipoR2 in HSCs followed by APN treatment demonstrated that AdipoR1 and AdipoR2 did not affect proliferation or TIMP-1 gene expression, while AdipoR2 modulated Col1-α1 and α-SMA gene expression, HSC migration, and AMPK activity. These finding suggest that AdipoR2 is the major APN receptor on HSCs responsible for mediating its anti-fibrotic effects.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ADIPOR2HumanExperimental Liver Cirrhosis severityISOAdipor2 (Mus musculus) RGD 
Adipor2RatExperimental Liver Cirrhosis severityISOAdipor2 (Mus musculus) RGD 
Adipor2MouseExperimental Liver Cirrhosis severityIMP  RGD 

Gene-Chemical Interaction Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MMP9Humantetrachloromethane increases expression ISOMmp9 (Mus musculus)CCl4 increases expression of mmp9 mRNA in Adipor2 KO mouse liverRGD 
Mmp9Rattetrachloromethane increases expression ISOMmp9 (Mus musculus)CCl4 increases expression of mmp9 mRNA in Adipor2 KO mouse liverRGD 
Mmp9Mousetetrachloromethane increases expression EXP CCl4 increases expression of mmp9 mRNA in Adipor2 KO mouse liverRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Adipor2Ratnegative regulation of gene expression  IMP  RGD 
Adipor2Ratnegative regulation of hepatic stellate cell migration  IMP  RGD 
Adipor2Ratpositive regulation of protein phosphorylation  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Adipor2  (adiponectin receptor 2)
Mmp9  (matrix metallopeptidase 9)

Genes (Mus musculus)
Adipor2  (adiponectin receptor 2)
Mmp9  (matrix metallopeptidase 9)

Genes (Homo sapiens)
ADIPOR2  (adiponectin receptor 2)
MMP9  (matrix metallopeptidase 9)


Additional Information