Pathogenetic mechanisms in radiation fibrosis.

Details

Serval ID
serval:BIB_DB40DED12177
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Title
Pathogenetic mechanisms in radiation fibrosis.
Journal
Radiotherapy and oncology
Author(s)
Yarnold J., Brotons M.C.
ISSN
1879-0887 (Electronic)
ISSN-L
0167-8140
Publication state
Published
Issued date
10/2010
Peer-reviewed
Oui
Volume
97
Number
1
Pages
149-161
Language
english
Notes
Publication types: Journal Article ; Review
Publication Status: ppublish
Abstract
Deregulation of normal regenerative responses to physical, chemical and biological toxins in susceptible individuals leads to abnormal remodelling of extracellular matrix with pathological fibrosis. Processes deregulated after radiotherapy have much in common with processes associated with fibrotic diseases affecting the heart, skin, lungs, kidneys, gastro-intestinal tract and liver. Among the secreted factors driving fibrosis, transforming growth factor beta 1 (TGFβ1) produced by a wide range of inflammatory, mesenchymal and epithelial cells converts fibroblasts and other cell types into matrix-producing myofibroblasts. Even if required for the initiation of fibrosis, inflammation and the continued stimulus of TGFβ1 may not be needed to maintain it. After myofibroblast activation, collagen production can be perpetuated independently of TGFβ1 by autocrine induction of a cytokine called connective tissue growth factor. The role of inflammation, the origins and activation of myofibroblasts as biosynthetic cells and the downstream pathways of extracellular matrix synthesis in common fibrotic states are reviewed. Oxidative stress, hypoxia and microvascular damage are also considered, before examining the same processes in the context of radiotherapy. One of the main uncertainties is the relevance of very early events, including inflammatory responses in blood vessels, to fibrosis. Despite the power of animal models, including genetic systems, the potential contribution of research based on human tissue samples has never been greater. A closer interaction between scientists researching fibrosis and radiation oncologists holds enormous promise for therapeutic advances.

Keywords
Atherosclerosis/etiology, Atherosclerosis/pathology, Extracellular Matrix/radiation effects, Fibrosis/etiology, Fibrosis/pathology, Humans, Myofibroblasts, Phenotype, Pulmonary Fibrosis/etiology, Pulmonary Fibrosis/pathology, Radiation Injuries/etiology, Radiation Injuries/pathology, Radiotherapy/adverse effects, Risk Factors, Scleroderma, Systemic/etiology, Scleroderma, Systemic/pathology
Pubmed
Web of science
Create date
30/04/2018 15:08
Last modification date
20/08/2019 16:00
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