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


CONCLUSIONS
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.
Seong
J
J
Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University Medical College, Seoul, Korea.
Kim
S H
SH
Chung
E J
EJ
Lee
W J
WJ
Suh
C O
CO
D000818:Animals; D015415:Biomarkers; D008099:Liver / Q000378:metabolism / Q000528:radiation effects*; D008106:Liver Cirrhosis, Experimental / Q000209:etiology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism / Q000528:radiation effects*; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000209:etiology; D011853:Radiobiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000528:radiation effects*
D015415:Biomarkers; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta