Titre
Molecular aspects of intestinal radiation-induced fibrosis.
Type
synthèse (review)
Institution
Externe
Périodique
Auteur(s)
Gervaz, P.
Auteure/Auteur
Morel, P.
Auteure/Auteur
Vozenin-Brotons, M.C.
Auteure/Auteur
Liens vers les personnes
ISSN
1566-5240
Statut éditorial
Publié
Date de publication
2009-04
Volume
9
Numéro
3
Première page
273
Dernière page/numéro d’article
280
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Review
Publication Status: ppublish
Publication Status: ppublish
Résumé
Radiation therapy is a key component of the management of various pelvic tumors, including prostate, gynecological, and anorectal carcinomas. Unfortunately, normal tissues located in the vicinity of target organs are radiosensitive, and long-term cancer survivors may develop late treatment-related injury, most notably radiation-induced fibrosis (RIF) of the small bowel. The cellular mediators of intestinal fibrosis are mesenchymal cells (i.e. myofibroblasts, fibroblasts and smooth muscle cells) which, when activated, serve as the primary collagen-producing cells, and are responsible for excess deposition of extracellular matrix components, eventually leading to intestinal loss of function. For decades, the underlying mechanisms involved in chronic activation of myofibroblasts within the normal tissues were unknown, and the fibrotic process, which ensued, was considered irreversible. Recent advances in the pathogenesis of RIF have demonstrated prolonged upregulation of fibrogenic cytokines, such as Transforming growth factor-beta1 (TGF-beta1) and its main downstream effector, Connective tissue growth factor (CTGF), in the myofibroblasts of irradiated small bowel. TGF-beta1-mediated activation of CTGF gene expression is controlled by Smads, but recently Rho/ROCK signaling has emerged as an alternative pathway involved in the control of CTGF expression in intestinal fibrosis. This article underlines the clinical relevance of RIF as it relates to damage to the small bowel, provides insight to its molecular biology, and finally unveils the potential role of Rho-ROCK inhibitors as emerging strategies to promote RIF reversal.
Sujets
PID Serval
serval:BIB_FF864764319B
PMID
Date de création
2018-04-30T14:01:21.494Z
Date de création dans IRIS
2025-05-21T06:29:12Z