RT Generic
T1 Mapping the CRF-urocortins system in human osteoarthritic and rheumatoid synovial fibroblasts: Effect of vasoactive intestinal peptide
A1 Pérez García, Selene
A1 Juarranz Moratilla, Yasmina
A1 Carrión Caballo, Mar
A1 Gutiérrez Cañas, Irene
A1 Margioris, Andrew
A1 Pablos Álvarez, José Luis
A1 Tsatsanis, Christos
A1 Pérez Gomáriz, Rosa María
AB In addition to the brain and pituitary gland, the corticotrophin-releasing factor (CRF) system is expressed in peripheral tissues. In this study we characterize the expression of CRF, urocortins (UCN1, UCN2, and UCN3), and their receptors (CRFR1 and CRFR2) in osteoarthritis (OA) and rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS). Moreover, we analyze the vasoactive intestinal peptide (VIP) effect on the CRF system, as well as its physiological consequences on mediators of inflammatory/destructive processes. CRF and UCNs exhibit differential pattern in OA and RA-FLS. By real-time PCR we detected more expression of CRF and UCN1 in RA, and UCN2 and UCN3 in OA, while the CRFR2 expression was similar. In RA-FLS VIP treatment resulted in a significant decrease of the proinflammatory peptides, CRF and UCN1, and a significant increase of the potential anti-inflammatory agents, UCN3 and CRFR2. Using Western blot assays, we showed that the ratio between phospho-CREB (p-CREB) and c-AMP response element-binding (CREB) is higher in OA and significantly lower in RA-FLS after VIP treatment, with consequences upon cAMP response element in CRF and UCN1 genes. Real-time PCR and EIA proved that VIP significantly inhibits cycloxygenase-2 (COX-2) and prostaglandin E2 (PGE2) in RA-FLS. In all cases, we consider significant data when P<0.05. These data indicate a role of endogenous CRF, UCNs, and CRFR2 in the OA and RA joint microenvironment. We confirm the anti-inflammatory function of VIP, through the modulation of the expression of CRF system that impacts in a reduction of mediators with inflammatory/destructive functions, supporting its therapeutic potential in rheumatic diseases.
PB Wiley
SN 0021-9541
YR 2011
FD 2011
LK https://hdl.handle.net/20.500.14352/93680
UL https://hdl.handle.net/20.500.14352/93680
LA eng
NO Pérez-García, Selene, et al. «Mapping the CRF-Urocortins System in Human Osteoarthritic and Rheumatoid Synovial Fibroblasts: Effect of Vasoactive Intestinal Peptide». Journal of Cellular Physiology, vol. 226, n.o 12, diciembre de 2011, pp. 3261-69. https://doi.org/10.1002/jcp.22687.
NO This work was supported by grants PI080025, RETICS Program, RD08/0075 (RIER) from the Instituto de Salud Carlos III (ISCIII), within VI PNDE IRDRI 2008/2011 and by FEDER funds, GR58/08 from UCM-BSCH and a predoctoral fellowship from theMinisterio de Ciencia e Innovacion.
NO Instituto de Salud Carlos III
NO European Commission
NO Ministerio de Ciencia e Innovación (España)
DS Docta Complutense
RD 9 abr 2025