Early alteration in TGF-β mRNA expression in irradiated rat liver

Purpose: Radiation of the liver results in hepatic fibrosis as a late complication. TGF-beta has been implicated in the pathogenesis of fibrosis, The purpose of this study was to determine if there is early alteration in TGF-beta expression before hepatic fibrosis is evident, Methods and Materials: Male Sprague-Dawley rats weighing 158-175 g were used. A partial volume of liver as large as a 2 cm x 1 cm rectangle was given a single dose of 25 Gy gamma radiation. Animals were sequentially sacrificed from day 0 to day 28, Appearance of hepatic fibrosis was tested by trichrome stain. Levels of mRNA expression of TGF-beta 1 and TGF-beta 3 were measured by Northern blot hybridization, Change in the level of mRNA expression was analyzed by densitometry, The expression of TGF-beta s was also analyzed in tissue with immunohistochemical staining. Results: In trichrome-stained liver tissues obtained through 28 days after irradiation, there was no evidence of hepatic fibrosis, The expression of mRNAs of TGF-beta 1 and TGF-beta 3 showed different features; The level of TGF-beta 1 mRNA showed a gradual increase to the peak level of 3.6-fold at day 28, the last analyzed time. In contrast, TGF-beta 3 mRNA showed an early peak of 4.8-fold at day 7 followed by a decrease to the lowest level of 1.6-fold at the last analyzed time. The expression of TGF-beta s was also analyzed in tissue with immunohistochemical staining. At day 28 after radiation, increased positive staining for TGF-beta 1 was observed around the central vein. Positive staining appeared mainly in nonhepatocytic cells. For TGF-beta 3, the same pattern of positive staining was observed at day 7, Conclusion: The results of this study suggest that the alteration in mRNA expression of TGF-beta 1 and TGF-beta 3 occurs very early after radiation. The contrasting difference in the mRNA expression pattern of TGF-beta 1 and TGF-beta 3 suggests that interaction of the TGF-Ps may be involved in fibrogenesis of irradiated liver, with TGF-beta 1 as a positive regulator and TGF-beta 3 as a negative regulator. (C) 2000 Elsevier Science Inc.