RGD Reference Report - Role of plasma kallikrein-kinin system activation in synovial recruitment of endothelial progenitor cells in experimental arthritis. - Rat Genome Database

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Role of plasma kallikrein-kinin system activation in synovial recruitment of endothelial progenitor cells in experimental arthritis.

Authors: Dai, J  Agelan, A  Yang, A  Zuluaga, V  Sexton, D  Colman, RW  Wu, Y 
Citation: Dai J, etal., Arthritis Rheum. 2012 Nov;64(11):3574-82. doi: 10.1002/art.34607.
RGD ID: 7297047
Pubmed: PMID:22739815   (View Abstract at PubMed)
PMCID: PMC3477304   (View Article at PubMed Central)
DOI: DOI:10.1002/art.34607   (Journal Full-text)

OBJECTIVE: To examine whether activation of the plasma kallikrein-kinin system (KKS) mediates synovial recruitment of endothelial progenitor cells (EPCs) in arthritis. METHODS: EPCs were isolated from Lewis rat bone marrow, and expression of progenitor cell-lineage markers and functional properties were characterized. EPCs were injected intravenously into Lewis rats with arthritis, and their recruitment and formation of de novo blood vessels in inflamed synovium were evaluated. The role of plasma KKS was examined using a plasma kallikrein inhibitor (EPI-KAL2) and an antikallikrein antibody (13G11). A transendothelial migration assay was used to determine the role of bradykinin and its receptor in EPC mobilization. RESULTS: EPCs from Lewis rats exhibited a strong capacity to form tubes and vacuoles and expressed increased levels of bradykinin type 2 receptor (B2R) and progenitor cell markers CD34 and Sca-1. In Lewis rats with arthritis, EPCs were recruited into inflamed synovium at the acute phase of disease and formed de novo blood vessels. Inhibition of plasma kallikrein by EPI-KAL2 and 13G11 significantly suppressed synovial recruitment of EPCs and hyperproliferation of synovial cells. Bradykinin stimulated transendothelial migration of EPCs in a concentration-dependent manner. This was mediated by B2R, as demonstrated by the finding that knockdown of B2R with silencing RNA completely blocked bradykinin-stimulated transendothelial migration. Moreover, bradykinin selectively up-regulated expression of the homing receptor CXCR4 in EPCs. CONCLUSION: These observations demonstrate a novel role of plasma KKS activation in the synovial recruitment of EPCs in arthritis, acting via kallikrein activation and B2R-dependent mechanisms. B2R might be involved in the mobilization of EPCs via up-regulation of CXCR4.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
KLKB1HumanExperimental Arthritis  ISOKlkb1 (Rattus norvegicus) RGD 
Klkb1MouseExperimental Arthritis  ISOKlkb1 (Rattus norvegicus) RGD 
Klkb1RatExperimental Arthritis  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Klkb1  (kallikrein B1)

Genes (Mus musculus)
Klkb1  (kallikrein B, plasma 1)

Genes (Homo sapiens)
KLKB1  (kallikrein B1)


Additional Information