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Early alteration in TGF-beta mRNA expression in irradiated rat liver.

 Jinsil Seong  ;  Sung Hee Kim  ;  Eun Ji Chung  ;  Won Jae Lee  ;  Chang Ok Suh 
 International Journal of Radiation Oncology Biology Physics, Vol.46(3) : 639-643, 2000 
Journal Title
 International Journal of Radiation Oncology Biology Physics 
Issue Date
Animals ; Biomarkers ; Liver/metabolism ; Liver/radiation effects* ; Liver Cirrhosis, Experimental/etiology ; Male ; RNA, Messenger/metabolism ; RNA, Messenger/radiation effects* ; Radiation Dosage ; Radiation Injuries, Experimental/etiology ; Radiobiology ; Rats ; Rats, Sprague-Dawley ; Time Factors ; Transforming Growth Factor beta/metabolism ; Transforming Growth Factor beta/radiation effects*
Radiation-induced hepatic fibrosis ; TGF-β1 ; TGF-β3
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 150-175 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-beta1 and TGF-beta3 were measured by Northern blot hybridization. Change in the level of mRNA expression was analyzed by densitometry. The expression of TGF-betas 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-beta1 and TGF-beta3 showed different features; The level of TGF-beta1 mRNA showed a gradual increase to the peak level of 3.6-fold at day 28, the last analyzed time. In contrast, TGF-beta3 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-betas was also analyzed in tissue with immunohistochemical staining. At day 28 after radiation, increased positive staining for TGF-beta1 was observed around the central vein. Positive staining appeared mainly in nonhepatocytic cells. For TGF-beta3, 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-beta1 and TGF-beta3 occurs very early after radiation. The contrasting difference in the mRNA expression pattern of TGF-beta1 and TGF-beta3 suggests that interaction of the TGF-betas may be involved in fibrogenesis of irradiated liver, with TGF-beta1 as a positive regulator and TGF-beta3 as a negative regulator.
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1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
Yonsei Authors
Seong, Jin Sil(성진실) ORCID logo https://orcid.org/0000-0003-1794-5951
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