Recombinant soluble transforming growth factor β type II receptor ameliorates radiation enteropathy in mice

  • Zheng H
  • Wang J
  • Koteliansky V
 et al. 
  • 12


    Mendeley users who have this article in their library.
  • 89


    Citations of this article.


Background & Aims: Transforming growth factor (TGF)-β 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-β type II receptor (TβR-ll) protein ameliorates intestinal radiation injury (radiation enteropathy). Methods: A recombinant fusion protein, consisting of the extracellular portion of mouse TβR-ll and the Fc portion of mouse immunoglobulin (lg) G, was produced. A 5-cm segment of mouse ileum was exposed to 19 Gy x-radiation. TβRll: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-β 1 messenger RNA was assessed with fluorogenic probe reverse-transcription polymerase chain reaction. Results: Compared with IgG controls, TβR-ll:Fc-treated mice exhibited less structural injury, preservation of mucosal surface area, and less intestinal wall fibrosis. Intestinal TGF-β l messenger RNA increased in TβR-ll:Fc-treated mice, whereas TGF-β immunoreactivity decreased. TβR-ll:Fc treatment increased crypt cell proliferation but otherwise did not affect unirradiated intestine. Conclusions: Long-term modulation of TGF-β with a TβR-ll:Fc fusion protein is feasible and ameliorates radiation enteropathy. These data confirm the putative role of TGF-β in intestinal radiation fibrosis. © 2000 by the American Gastroenterological Association.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document


  • Huaien Zheng

  • Junru Wang

  • Victor E. Koteliansky

  • Philip J. Gotwals

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free