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CD47 regulates coll...
CD47 regulates collagen I-induced cyclooxygenase-2 expression and intestinal epithelial cell migration.
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- Broom, Oliver (author)
- Lund University,Lunds universitet,Cellpatologi, Malmö,Forskargrupper vid Lunds universitet,Cell Pathology, Malmö,Lund University Research Groups
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- Zhang, Yuan (author)
- Lund University,Lunds universitet,Cellpatologi, Malmö,Forskargrupper vid Lunds universitet,Cell Pathology, Malmö,Lund University Research Groups
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- Oldenborg, Per-Arne (author)
- Umeå universitet,Institutionen för integrativ medicinsk biologi (IMB)
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- Massoumi, Ramin (author)
- Lund University,Lunds universitet,Cellpatologi, Malmö,Forskargrupper vid Lunds universitet,Cell Pathology, Malmö,Lund University Research Groups
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- Sjölander, Anita (author)
- Lund University,Lunds universitet,Cellpatologi, Malmö,Forskargrupper vid Lunds universitet,Cell Pathology, Malmö,Lund University Research Groups
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(creator_code:org_t)
- 2009-07-28
- 2009
- English.
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In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 4:7, s. e6371-
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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