RGD Reference Report - Urocortin promotes the development of vasculitis in a rat model of thromboangiitis obliterans via corticotrophin-releasing factor type 1 receptors. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Urocortin promotes the development of vasculitis in a rat model of thromboangiitis obliterans via corticotrophin-releasing factor type 1 receptors.

Authors: Xu, Y  Zhang, R  Chen, J  Zhang, Q  Wang, J  Hu, J  Guan, X  Jin, L  Fu, H  Gui, B  Guo, Y  Li, S 
Citation: Xu Y, etal., Br J Pharmacol. 2009 Aug;157(8):1368-79. Epub 2009 Jun 30.
RGD ID: 5508315
Pubmed: (View Article at PubMed) PMID:19572944
DOI: Full-text: DOI:10.1111/j.1476-5381.2009.00210.x

BACKGROUND AND PURPOSE: Urocortin is a locally expressed pro-inflammatory peptide. Here we have examined the effects of urocortin on sodium laurate-induced peripheral arterial vasculitis in rats, modelling the mechanisms of thromboangiitis obliterans (TAO). EXPERIMENTAL APPROACH: Peripheral vasculitis in rats was induced by sodium laurate and graded by gross appearance on the 12th day after injection. Histological changes in rat femoral arteries were assessed by histopathology and transmission electron microscopy. Blood cell counts, blood rheology, blood coagulation and plasma urocortin, thromboxane B(2), prostaglandin E(2) and soluble intercellular adhesion molecule-1 levels were measured. Expression of urocortin, corticotrophin-releasing factor (CRF(1/2)) receptors, cyclooxygenase (COX)-2 and intercellular adhesion molecule-1 (ICAM-1) at both mRNA and protein levels were determined by RT-PCR and Western blot. KEY RESULTS: Rats showed grossly visible signs and symptoms of TAO on the 12th day after sodium laurate injection. In these rats, blood was in a hypercoagulable state; plasma urocortin, prostaglandin E(2) and soluble intercellular adhesion molecule-1 levels were elevated; and the expression of urocortin, CRF(1) and CRF(1alpha)-receptors, COX-2 and ICAM-1 in rat femoral arteries were markedly increased. Exogenous urocortin, given for 12 days after sodium laurate, exacerbated the hypercoagulable state and augmented expression of CRF(1alpha)-receptors, COX-2 and ICAM-1. These effects were abolished by a CRF(1)-receptor antagonist, NBI-27914, or a non-selective CRF-receptor antagonist, astressin, but not by the CRF(2)-receptor antagonist, antisauvagine-30, given with exogenous urocortin. CONCLUSION AND IMPLICATIONS: Urocortin exacerbated the hypercoagulable state and vasculitis in a model of TAO induced by sodium laurate in rats, via CRF(1)-receptors. COX-2 and ICAM-1 might also have contributed to this exacerbation.

Annotation

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Crhr1  (corticotropin releasing hormone receptor 1)
Ucn  (urocortin)

Genes (Mus musculus)
Crhr1  (corticotropin releasing hormone receptor 1)
Ucn  (urocortin)

Genes (Homo sapiens)
CRHR1  (corticotropin releasing hormone receptor 1)
UCN  (urocortin)


Additional Information