CD47 regulates collagen I-induced cyclooxygenase-2 expression and intestinal epithelial cell migration.
2009 (English)In: PloS one, ISSN 1932-6203, Vol. 4, no 7, e6371- p.Article in journal (Refereed) Published
Increased epithelial cell expression of the cyclooxygenase-2 (COX-2) enzyme is a characteristic event of both inflammatory bowel disease and colon cancer. We here report the novel findings that collagen I-induced de novo synthesis of COX-2 in intestinal epithelial cells is inhibited by pertussis toxin (PTX) and by an inhibitory peptide selective for the heterotrimeric G alpha(i3)-protein. These findings could be explained by a regulatory involvement of the G-protein-dependent integrin-associated protein CD47. In support of this notion, we observed a collagen I-induced association between CD47 and alpha2 integrins. This association was reduced by a blocking anti-CD47 antibody but not by PTX or a control anti-beta2 antibody. Furthermore, a blocking antibody against CD47, dominant negative CD47 or specific siRNA knock down of CD47, significantly reduced collagen I-induced COX-2 expression. COX-2 has previously been shown to regulate intestinal epithelial cell adhesion and migration. Morphological analysis of intestinal cells adhering to collagen I revealed a co-localisation of CD47 and alpha2 integrins to non-apoptotic membrane blebs enriched in Rho A and F-actin. The blocking CD47 antibody, PTX and a selective COX-2 inhibitor, dramatically inhibited the formation of these blebs. In accordance, migration of these cells on a collagen I-coated surface or through a collagen I gel were significantly reduced by the CD47 blocking antibody, siRNA knock down of CD47 and the COX-2 inhibitor NS-398. In conclusion, we present novel data that identifies the G-protein-dependent CD47 protein as a key regulator of collagen I-induced COX-2 expression and a promoter of intestinal epithelial cell migration.
Place, publisher, year, edition, pages
2009. Vol. 4, no 7, e6371- p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:umu:diva-32000DOI: 10.1371/journal.pone.0006371PubMedID: 19636412OAI: oai:DiVA.org:umu-32000DiVA: diva2:301395