TGF-beta 1 and radiation fibrosis: A master switch and a specific therapeutic target?

Radiation fibrosis is a frequent sequel of therapeutic or accidental radiat ion overexposure in normal human tissues. One of the main fundamental probl ems yet unsolved in fibrotic tissues is the origin of the chronic activatio n of myofibroblasts within these tissues. It has been postulated that this chronic activation results from a continuous production of activating facto rs. In this context, fibrosis could be defined as a wound where continuous signals for tissue repair are emitted. Cytokines and growth factors probabl y play a central role in this process, Among them, transforming growth fact or-beta 1 (TGF-beta 1) is considered as a master switch for the fibrotic pr ogram. This review discusses recent evidence on the critical role played by TGF-beta in the initiation, development, and persistence of radiation fibr osis, It summarizes the results concerning this factor after irradiation of various tissues and cells, with an emphasis on superficial fibrosis, inclu ding skin and subcutaneous tissues, Finally, recent data concerning the tre atment of established fibrotic disorders of various etiology are presented, as well as the possible mechanisms involved in fibrosis regression, which show that the TGF-beta pathway may constitute a specific target for antifib rotic agents. (C) 2000 Elsevier Science Inc.