RGD Reference Report - The role of CX(3)CL1/CX(3)CR1 in pulmonary angiogenesis and intravascular monocyte accumulation in rat experimental hepatopulmonary syndrome. - Rat Genome Database

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The role of CX(3)CL1/CX(3)CR1 in pulmonary angiogenesis and intravascular monocyte accumulation in rat experimental hepatopulmonary syndrome.

Authors: Zhang, J  Yang, W  Luo, B  Hu, B  Maheshwari, A  Fallon, MB 
Citation: Zhang J, etal., J Hepatol. 2012 Oct;57(4):752-8. doi: 10.1016/j.jhep.2012.05.014. Epub 2012 May 29.
RGD ID: 9491778
Pubmed: PMID:22659346   (View Abstract at PubMed)
PMCID: PMC3667409   (View Article at PubMed Central)
DOI: DOI:10.1016/j.jhep.2012.05.014   (Journal Full-text)

BACKGROUND & AIMS: Hepatopulmonary syndrome (HPS), classically attributed to intrapulmonary vascular dilatation, occurs in 15-30% of cirrhotics and causes hypoxemia and increases mortality. In experimental HPS after common bile duct ligation (CBDL), monocytes adhere in the lung vasculature and produce vascular endothelial growth factor (VEGF)-A and angiogenesis ensues and contribute to abnormal gas exchange. However, the mechanisms for these events are unknown. The chemokine fractalkine (CX(3)CL1) can directly mediate monocyte adhesion and activate VEGF-A and angiogenesis via its receptor CX(3)CR1 on monocytes and endothelium during inflammatory angiogenesis. We explored whether pulmonary CX(3)CL1/CX(3)CR1 alterations occur after CBDL and influence pulmonary angiogenesis and HPS. METHODS: Pulmonary CX(3)CL1/CX(3)CR1 expression and localization, CX(3)CL1 signaling pathway activation, monocyte accumulation, and development of angiogenesis and HPS were assessed in 2- and 4-week CBDL animals. The effects of a neutralizing antibody to CX(3)CR1 (anti-CX(3)CR1 Ab) on HPS after CBDL were evaluated. RESULTS: Circulating CX(3)CL1 levels and lung expression of CX(3)CL1 and CX(3)CR1 in intravascular monocytes and microvascular endothelium increased in 2- and 4-week CBDL animals as HPS developed. These events were accompanied by pulmonary angiogenesis, monocyte accumulation, activation of CX(3)CL1 mediated signaling pathways (Akt, ERK) and increased VEGF-A expression and signaling. Anti-CX(3)CR1 Ab treatment reduced monocyte accumulation, decreased lung angiogenesis and improved HPS. These events were accompanied by inhibition of CX(3)CL1 signaling pathways and a reduction in VEGF-A expression and signaling. CONCLUSIONS: Circulating CX(3)CL1 levels and pulmonary CX(3)CL1/CX(3)CR1 expression and signaling increase after CBDL and contribute to pulmonary intravascular monocyte accumulation, angiogenesis and development of experimental HPS.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hepatopulmonary syndrome  ISOCx3cl1 (Rattus norvegicus)9491778; 9491778protein:increased expression:lung and plasmaRGD 
hepatopulmonary syndrome treatmentISOCx3cr1 (Rattus norvegicus)9491778; 9491778 RGD 
hepatopulmonary syndrome  IEP 9491778protein:increased expression:lung and plasmaRGD 
hepatopulmonary syndrome treatmentIMP 9491778 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of angiogenesis  IMP 9491778 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cx3cl1  (C-X3-C motif chemokine ligand 1)
Cx3cr1  (C-X3-C motif chemokine receptor 1)

Genes (Mus musculus)
Cx3cl1  (C-X3-C motif chemokine ligand 1)
Cx3cr1  (C-X3-C motif chemokine receptor 1)

Genes (Homo sapiens)
CX3CL1  (C-X3-C motif chemokine ligand 1)
CX3CR1  (C-X3-C motif chemokine receptor 1)


Additional Information