Influence of endothelial cells on vascular smooth muscle cells phenotype after irradiation: implication in radiation-induced vascular damages.

Details

Serval ID
serval:BIB_B2CBD69D8EDE
Type
Article: article from journal or magazin.
Collection
Publications
Title
Influence of endothelial cells on vascular smooth muscle cells phenotype after irradiation: implication in radiation-induced vascular damages.
Journal
American Journal of Pathology
Author(s)
Milliat F., François A., Isoir M., Deutsch E., Tamarat R., Tarlet G., Atfi A., Validire P., Bourhis J., Sabourin J.C., Benderitter M.
ISSN
0002-9440 (Print)
ISSN-L
0002-9440
Publication state
Published
Issued date
2006
Peer-reviewed
Oui
Volume
169
Number
4
Pages
1484-1495
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Abstract
Damage to vessels is one of the most common effects of therapeutic irradiation on normal tissues. We undertook a study in patients treated with preoperative radiotherapy and demonstrated in vivo the importance of proliferation, migration, and fibrogenic phenotype of vascular smooth muscle cells (VSMCs) in radiation-induced vascular damage. These lesions may result from imbalance in the cross talk between endothelial cells (ECs) and VSMCs. Using co-culture models, we examined whether ECs influence proliferation, migration, and fibrogenic phenotype of VSMCs. In the presence of irradiated ECs, proliferation and migration of VSMCs were increased. Moreover, expressions of alpha-smooth muscle actin, connective tissue growth factor, plasminogen activator inhibitor type 1, heat shock protein 27, and collagen type III, alpha 1 were up-regulated in VSMCs exposed to irradiated ECs. Secretion of transforming growth factor (TGF)-beta1 was increased after irradiation of ECs, and irradiated ECs activated the Smad pathway in VSMCs by inducing Smad3/4 nuclear translocation and Smad-dependent promoter activation. Using small interferring RNA targeting Smad3 and a TGFbeta-RII neutralizing antibody, we demonstrate that a TGF-beta1/TGF-beta-RII/Smad3 pathway is involved in the fibrogenic phenotype of VSMCs induced by irradiated ECs. In conclusion, we show the importance of proliferation, migration, and fibrogenic phenotype of VSMCs in patients. Moreover, we demonstrate in vitro that ECs influence these fundamental mechanisms involved in radiation-induced vascular damages.
Keywords
Actins/analysis, Actins/metabolism, Adenocarcinoma/radiotherapy, Cell Movement, Cell Proliferation, Coculture Techniques, Collagen Type I/analysis, Collagen Type I/metabolism, Collagen Type III/analysis, Collagen Type III/metabolism, Connective Tissue Growth Factor, Endothelium, Vascular/pathology, Endothelium, Vascular/radiation effects, Fibrinogen/metabolism, Gamma Rays, Heat-Shock Proteins/analysis, Heat-Shock Proteins/metabolism, Humans, Immediate-Early Proteins/analysis, Immediate-Early Proteins/metabolism, Intercellular Signaling Peptides and Proteins/analysis, Intercellular Signaling Peptides and Proteins/metabolism, Muscle, Smooth, Vascular/pathology, Myocytes, Smooth Muscle/chemistry, Myocytes, Smooth Muscle/metabolism, Phenotype, Plasminogen Activator Inhibitor 1/analysis, Plasminogen Activator Inhibitor 1/metabolism, Radiation Injuries/pathology, Rectal Neoplasms/radiotherapy, Smad2 Protein/analysis, Smad2 Protein/metabolism, Smad3 Protein/analysis, Smad3 Protein/metabolism, Transforming Growth Factor beta/analysis, Transforming Growth Factor beta/metabolism, Up-Regulation, Vascular Diseases/pathology
Pubmed
Web of science
Create date
01/12/2014 17:32
Last modification date
20/08/2019 15:21
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