Fibrogenic signals in patients with radiation enteritis are associated with increased connective tissue growth factor expression.

Details

Serval ID
serval:BIB_15D841A8F4B0
Type
Article: article from journal or magazin.
Collection
Publications
Title
Fibrogenic signals in patients with radiation enteritis are associated with increased connective tissue growth factor expression.
Journal
International Journal of Radiation Oncology, Biology, Physics
Author(s)
Vozenin-Brotons M.C., Milliat F., Sabourin J.C., de Gouville A.C., François A., Lasser P., Morice P., Haie-Meder C., Lusinchi A., Antoun S., Bourhis J., Mathé D., Girinsky T., Aigueperse J.
ISSN
0360-3016 (Print)
ISSN-L
0360-3016
Publication state
Published
Issued date
2003
Peer-reviewed
Oui
Volume
56
Number
2
Pages
561-572
Language
english
Notes
Publication types: Journal Article Publication Status: ppublish
Abstract
PURPOSE: To investigate the expression of a new fibrogenic cytokine the connective tissue growth factor (CTGF) in intestinal radiation fibrosis and to characterize the mesenchymal cell subtypes involved in CTGF synthesis and collagen deposition.
METHODS AND MATERIALS: Sixteen patients with radiation enteritis that occurred after radiotherapy for pelvic malignancies and 6 with histologically normal bowel entered the study. Immunohistochemistry, Western blot analysis, and real-time reverse transcriptase-polymerase chain reaction were performed to study CTGF expression, along with other known markers of radiation fibrosis: the pro-fibrogenic cytokine transforming growth factor (TGF)-beta1 and phenotypic markers of the fibroblast differentiation the alpha-sm actin (A), vimentin (V), and desmin (D). Finally, the collagen accumulation was measured by Sirius red staining and colorimetric assay.
RESULTS: Radiation enteritis was characterized by increased collagen content within the intestinal wall. CTGF immunoreactivity, protein, and mRNA level were increased in radiation enteritis compared with the healthy bowel. On the contrary, no increase of the TGF-beta1 mRNA level was observed in radiation enteritis compared with healthy bowel, and the level of TGF-beta protein was slightly increased in radiation enteritis. A co-localization of CTGF immunoreactivity and collagen deposition was found in the extracellular matrix and subtypes of activated mesenchymal cells with a fibroblast phenotype (V(+)/D(-)/A(-)) and myofibroblast phenotype (V(+)/D(-/+)/A(+)).
CONCLUSION: The increased level of CTGF protein and mRNA associated with the accumulation of fibroblasts/myofibroblasts and collagen deposition were parts of the fibrogenic signals involved in the persistence of late intestinal radiation fibrosis.
Keywords
Adult, Aged, Biological Markers, Blotting, Northern, Collagen, Connective Tissue Growth Factor, Enteritis/metabolism, Female, Fibroblasts, Fibrosis/metabolism, Humans, Immediate-Early Proteins/metabolism, Intercellular Signaling Peptides and Proteins/metabolism, Male, Middle Aged, Phenotype, RNA, Messenger/metabolism, Radiation Injuries/metabolism
Pubmed
Web of science
Create date
01/12/2014 17:57
Last modification date
20/08/2019 12:45
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