Changes in Transforming Growth Factor beta1 Gene Expression and Immunoreactivity Levels During Development of Chronic Radiation Enteropathy

Radiat Res. 1998 Dec;150(6):673-80.

Abstract

Chronic intestinal radiation injury is associated with locally increased TGF-beta1 immunoreactivity that correlates with morphological alterations. However, the underlying mechanisms are not known. This study examined changes in intestinal TGF-beta1 immunoreactivity, steady-state TGF-beta1 mRNA levels, and cellular localization of TGF-beta1 mRNA during development of chronic radiation enteropathy in a rat model. A loop of small bowel was fixed inside the scrotum of orchiectomized male rats. The intestine was subsequently exposed locally to 0, 12 or 21 Gy X radiation. Intestine was procured at 24 h and 2, 6 and 26 weeks and subjected to histopathological analysis, quantitative immunohistochemistry with computerized image analysis, assessment of steady-state TGF-beta1 mRNA levels with quantitative reverse transcriptase polymerase chain reaction, and identification of cell types expressing TGF-beta1 mRNA with in situ hybridization. Intestine from the 21-Gy group exhibited more histopathological injury and increased TGF-beta immunoreactivity 2-26 weeks after irradiation compared to the 12-Gy group and sham-irradiated controls. TGF-beta1 mRNA in irradiated intestine increased up to six times relative to controls at 24 h and 2 weeks, was less at 6 weeks, and did not differ from controls at 26 weeks. In situ hybridization detected TGF-beta1 mRNA in epithelial and Paneth cells in control intestine. Irradiated intestine exhibited additional TGF-beta1 mRNA in inflammatory and fibroblast-like cells. We conclude that there is a radiation-induced shift in the cellular sources of TGF-beta1, and that Tgfb1 gene expression is increased mainly during the early phases of radiation enteropathy, preceding the increase in immunoreactivity and histopathological injury. Translational or post-translational mechanisms are likely involved in sustaining increased TGF-beta1 immunoreactivity levels during the chronic phase of radiation enteropathy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • DNA Primers / genetics
  • Gene Expression
  • Immunohistochemistry
  • In Situ Hybridization
  • Intestine, Small / immunology
  • Intestine, Small / injuries*
  • Intestine, Small / radiation effects*
  • Male
  • Protein Biosynthesis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Radiation Injuries, Experimental / etiology*
  • Radiation Injuries, Experimental / genetics
  • Radiation Injuries, Experimental / immunology
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transforming Growth Factor beta / genetics*
  • Transforming Growth Factor beta / metabolism*

Substances

  • DNA Primers
  • RNA, Messenger
  • Transforming Growth Factor beta