Abstract
Transforming growth factor (TGF)-beta has been implicated in many fibrotic conditions. However, its mechanistic role in radiation toxicity is equivocal despite compelling correlative evidence. This study assessed whether in vivo administration of a soluble TGF-beta type II receptor (TbetaR-II) protein ameliorates intestinal radiation injury (radiation enteropathy). A recombinant fusion protein, consisting of the extracellular portion of mouse TbetaR-II and the Fc portion of mouse immunoglobulin (Ig) G, was produced. A 5-cm segment of mouse ileum was exposed to 19 Gy x-radiation. TbetaR-II:Fc fusion protein (1 mg/kg every other day) or mouse IgG was administered from 2 days before to 6 weeks after irradiation. Radiation injury was assessed at 6 weeks using quantitative histology, morphometry, and immunohistochemistry. Collagen was measured colorimetrically, and TGF-beta1 messenger RNA was assessed with fluorogenic probe reverse-transcription polymerase chain reaction. Compared with IgG controls, TbetaR-II:Fc-treated mice exhibited less structural injury, preservation of mucosal surface area, and less intestinal wall fibrosis. Intestinal TGF-beta1 messenger RNA increased in TbetaR-II:Fc-treated mice, whereas TGF-beta immunoreactivity decreased. TbetaR-II:Fc treatment increased crypt cell proliferation but otherwise did not affect unirradiated intestine. Long-term modulation of TGF-beta with a TbetaR-II:Fc fusion protein is feasible and ameliorates radiation enteropathy. These data confirm the putative role of TGF-beta in intestinal radiation fibrosis.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.