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Journal of Histochemistry and Cytochemistry, Vol. 49, 121-130, January 2001, Copyright © 2001, The Histochemical Society, Inc.

ARTICLE

Expression and Role of Vascular Endothelial Growth Factor in Liver Regeneration After Partial Hepatectomy in Rats

Eitaro Taniguchia, Shotaro Sakisakaa, Katsuhiko Matsuob, Kyuichi Tanikawac, and Michio Sataa
a Second Department of Medicine and Kurume University Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Kurume, Japan
b Bioscience Research Department, Tsukuba Research Laboratory, Toagosei Co. Ltd., Tsukuba, Japan
c International Institute for Liver Research, Kurume, Japan

Correspondence to: Shotaro Sakisaka, Third Department of Medicine, Fukuoka University, Fukuoka, Japan. E-mail: sakisaka@fukuoka-u.ac.jp or eitaro@med.kurume-u.ac.jp

Vascular endothelial growth factor (VEGF) plays a major role in angiogenesis, which is essential for both healing of injured tissue and proliferation of carcinoma cells. In this study we elucidated the expression and role of VEGF in rat liver regeneration after partial hepatectomy. VEGF expression was mainly detected in periportal hepatocytes and reached a maximal level 48–72 hr after partial hepatectomy by both immunohistochemistry and in situ hybridization. Similarly, immunohistochemistry for Ki-67 showed that the proliferative activity of sinusoidal endothelial cells was highest in the periportal area and reached a maximal level 72 hr after partial hepatectomy. Moreover, neutralization of VEGF significantly inhibited proliferative activity of hepatocytes (p<0.0001), as well as sinusoidal endothelial cells (p<0.001), at 48 and 96 hr after partial hepatectomy. Conversely, injection of VEGF significantly promoted proliferative activity of hepatocytes (p<0.0001) as well as sinusoidal endothelial cells (p<0.0005) at 48 hr after partial hepatectomy. These results suggest that VEGF promotes proliferation of hepatocytes through reconstruction of liver sinusoids by proliferation of sinusoidal endothelial cells. Furthermore, these data point to a new therapeutic strategy, the use of VEGF and other hepatocyte growth factors in fulminant or severe acute hepatitis. (J Histochem Cytochem 49:121&NDASH;129, 2001)

Key Words: vascular endothelial growth, factor, liver regeneration, partial hepatectomy, sinusoidal endothelial cell, heterogeneity, Ki-67


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