Acinar Zonal Difference of Transforming Growth Factor B1 Expression in Rat Models of Selective Zonal Hepatic Necrosis

Lee, Young Sang; Chung, Young Hwa; Chang, Rin; Suh, Dong Jin; Song, Il Han; Kim, Hyung Geon; Koh, Moon Soo; Kim, Jeong A

Abstract

BACKGROUND AND AIMS: Transforming growth factor B1 (TGF B1) is a cytokine that has regulatory roles in cell growth and differentiation. Especially, this cytokine has been reported to be associated with hepatic fibrosis. The aim of this study was to assess the role of TGF B1 m the progression of early hepatic fibrosis.
METHODS
The periportal (50 rats) and centrilobular (50 rats) hepatic necrosis were induced by intraperitoneal injection of allylalcohol (0.62 mmol/g of BW) and bromobenzene (3.8 mmol/g of BW), respectively. We obtained the serum and liver tissue according to the time sequences after toxin administration. Besides the microscopic examination of liver tissue, we measured the serum alanine aminotransferase (ALT) activities and serum TGF B1 concentration. The expressions of liver TGF B1 mRNA were semiquantitated by reverse transcription polymerase chain reaction and end point dilution method. The results were calibrated by B-actin mRNA measured by northern blot hybridization.
RESULTS
In the groups of periportal necrosis, the serum ALT activities were increased maximally at 12 hours and thereafter progressively decreased, while in groups of centrilobular necrosis, ALT activties were progressively increased up to 48 hours. By toxin administration of single dose, the expression of TGF B1 were increased regardless of the site of hepatic necrosis. These amounts were maximally increased at 12 hours like seum ALT activities in groups of periportal necrosis. In the groups of centrilobular necrosis, the maximal expression of liver TGF beta1 mRNA and peak concentration of serum TGF beta1 were observed at 48 hours and 72 hours, respectively. The duration of TGF Dl expression was longer in the groups of centrilobular necrosis than in the groups of periportal necrosis.
CONCLUSIONS
The expression pattern of TGF beta1 was different according to the zonal difference of hepatic necrosis. Therefore, the mechanism and progression pattern of hepatic fibrosis may be different according to various causes of selective zonal injury.