SPATIAL AND TEMPORAL PATTERNS OF EXPRESSION OF EPIDERMAL GROWTH-FACTOR, TRANSFORMING GROWTH-FACTOR-ALPHA AND TRANSFORMING-GROWTH-FACTOR-BETA-1-3 AND THEIR RECEPTORS IN MOUSE JEJUNUM AFTER RADIATION TREATMENT

The goal of the present study was to assess changes in proliferation i n the mouse jejunum after irradiation and the role of the growth facto rs EGF, TGF-alpha and TGF-beta(1-3) in the proliferative response. Our working hypothesis was that feedback signals from the villus to cells in the crypt regulate proliferation, and that the growth factors EGF and TGF-alpha with their common receptor EGF-R are involved in stimula tion of proliferation, while the growth factors TGF-beta(1-3) with the ir receptors TGF-beta RI and TGF-beta RII are involved in inhibition o f proliferation during this regulation. Immunohistochemical detection methods and automated image analysis were used for objective quantific ation of growth factor expression. The data indicate that, after 5 Gy irradiation, growth stimulation in the crypts takes place before major changes in the villi are observed. However, the combination of the re duction in the cell number, the number of cells expressing TGF-beta(1- 3) and the reduction in the level of expression of TGF-beta(1-3) in th e villi may cause the release of crypt cells from regulatory growth in hibition and initiate a proliferation-stimulating signal by an increas e in the production of TGF-alpha and EGF. Regulation of proliferation after initiation of a proliferative response seems to be related more to the growth factors EGF, TGF-alpha and TGF-beta, in the crypts than to villus cellularity or growth factor expression, supporting the conc ept of stem cell autoregulation as a mechanism of cell regeneration in the intestinal crypt. (C) 1997 by Radiation Research Society