Regulators and mediators of radiation-induced fibrosis: Gene expression profiles and a rationale for Smad3 inhibition

We have characterized the early-phase mRNA expression profiles of the major mediators of radiation-induced fibrosis. Smad3 siRNA effectively abrogated the elevation of Col1A1, TGF-β, TIMP-1, and MMP-2. IL-13 and TNF-α were unaffected by Smad3 silencing and appear to be minor regulators in fibrosis. These findings suggest a therapeutic rationale for Smad3 silencing in vivo.