CD47 regulates collagen I-induced cyclooxygenase-2 expression and intestinal epithelial cell migration.
(2009) In PLoS ONE 4(7).- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1452727
- author
- Broom, Oliver LU ; Zhang, Yuan LU ; Oldenborg, Per-Arne ; Massoumi, Ramin LU and Sjölander, Anita LU
- organization
- publishing date
- 2009
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS ONE
- volume
- 4
- issue
- 7
- article number
- e6371
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- wos:000268404900007
- pmid:19636412
- scopus:68149138463
- ISSN
- 1932-6203
- DOI
- 10.1371/journal.pone.0006371
- language
- English
- LU publication?
- yes
- id
- 43bee155-852b-41fc-b843-6009d9eecbd8 (old id 1452727)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/19636412?dopt=Abstract
- date added to LUP
- 2016-04-04 09:34:49
- date last changed
- 2022-01-29 18:32:35
@article{43bee155-852b-41fc-b843-6009d9eecbd8,
abstract = {{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.}},
author = {{Broom, Oliver and Zhang, Yuan and Oldenborg, Per-Arne and Massoumi, Ramin and Sjölander, Anita}},
issn = {{1932-6203}},
language = {{eng}},
number = {{7}},
publisher = {{Public Library of Science (PLoS)}},
series = {{PLoS ONE}},
title = {{CD47 regulates collagen I-induced cyclooxygenase-2 expression and intestinal epithelial cell migration.}},
url = {{http://dx.doi.org/10.1371/journal.pone.0006371}},
doi = {{10.1371/journal.pone.0006371}},
volume = {{4}},
year = {{2009}},
}