Angiopoietin/Tie Receptors System may Play a Role During Reconstruction and Capillarization of the Hepatic Sinusoids after Partial Hepatectomy and Liver Necrosis in Rats.

血管生成素/领带受体系统可能在大鼠部分肝切除和肝坏死后肝窦的重建和毛细血管化过程中发挥作用。

• 批准号: 14570504
• 负责人: MATSUI Atsushi
• 金额: $ 2.24万
• 依托单位: Saitama Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570504/
• 关键词: Angiopoietin; Tie-2; Sinusoidal endothelial cells; Stellate cells; Kupffer cells; Sinusoids; Hepatectomized rats; Immunohistochemistry; 障害肝; 類洞; KUPFFER細胞

Sinusoidal endothelial cells and hepatocytes increase in number after partial resection and necrosis of the liver, and contribute to both reconstruction and capillarization of the sinusoids through interaction with stellate cells. The mechanism underling such interaction was evaluated regarding angiopoietins and Tie receptors essential for blood vessel formation. Hepatic mRNA expressions of angiopoietin-1, angiopoietin-2 and Tie-2 were increased at 168 hours after 70% liver resection with sinusoidal reconstruction in rats, and also at 48 hours with sinusoidal capillarization in the liver of rats given carbon tetrachloride(CC14). Tie-2 mRNA expression was detected in sinusoidal endothelial cells and stellate cells isolated from normal rats, and in activated stellate cells from CC14-intoxicated rats. The mRNA expressions of angiopoietin-1 and angiopoietin-2 were detectable in Kupffer cells, sinusoidal endothelial cells and stellate cells in normal rats, but increased in activated stellate cells and macrophages after CC14-intoxication. Both angiopoietins and Tie-2 were immunohistochemically stained along the sinusoids of 70% hepatectomized rats and in necrotic areas of CC14-intoxicated rats. Angiopoietin-1 and angiopoietin-2 may be involved in both reconstruction and capillarization of the sinusoids in rat liver after partial resection and necrosis through interaction between stellate cells and sinusoidal and vascular endothelial cells via Tie-2 receptor.

肝部分切除和坏死后，肝窦内皮细胞和肝细胞数量增多，并通过与星状细胞的相互作用促进肝窦的重建和毛细血管形成。关于血管生成所必需的血管生成素和TiE受体，对这种相互作用的机制进行了评估。大鼠肝切除后，血管生成素-1、血管生成素-2和Tie-2的mRNA表达在70%肝切除后168小时和四氯化碳(CC14)肝毛细血管形成后48小时显著增加。正常大鼠的肝窦内皮细胞和星状细胞以及CC14中毒大鼠活化的星状细胞中均有Tie-2mRNA的表达。正常大鼠Kupffer细胞、肝窦内皮细胞和星状细胞中均有血管生成素-1和血管生成素-2的表达，CC14中毒后活化的星状细胞和巨噬细胞中血管生成素-1和血管生成素-2的表达增强。血管生成素和Tie-2在70%肝切除大鼠的肝窦和CC14中毒大鼠的坏死区均有免疫组织化学染色。血管生成素-1和血管生成素-2可能通过Tie-2受体参与星状细胞与肝窦和血管内皮细胞的相互作用，参与肝窦部分切除和坏死后肝窦的重建和毛细血管形成。

项目成果

Mochida S, Hashimoto M, Matsui A, et l.: "Genetic Polymorphisms in Promoter Region of Osteopontin Gene as a Marker for Predicting Hepatitis Activity in Chronic Hepatitis C Patients"Biochem Biophys Res Commun. 313. 1079-1085 (2004)

Mochida S、Hashimoto M、Matsui A 等人：“骨桥蛋白基因启动子区域的基因多态性作为预测慢性丙型肝炎患者肝炎活动的标记”Biochem Biophys Res Commun。

Mimura S, Mochida S, Inao M, Matsui A, Nagoshi S, Yoshimoto T, Fujiwara K.: "Massive Liver Necrosis after Provocation of Imbalance between Th1 and Th2 Immune Reactions in Osteopontin Transgenic Mice."J Gastroenterol. (in press).

Mimura S、Mochida S、Inao M、Matsui A、Nagoshi S、Yoshimoto T、Fujiwara K.：“骨桥蛋白转基因小鼠中 Th1 和 Th2 免疫反应失衡后引起大面积肝坏死。”J Gastroenterol。

Mimura S, Mochida S, Inao M, et al.: "Massive Liver Necrosis after Provocation of Imbalance between Th1 and Th2 Immune Reactions in Osteopontin Transgenic Mice"J Gastroenterol. (in press).

Mimura S、Mochida S、Inao M 等人：“骨桥蛋白转基因小鼠中 Th1 和 Th2 免疫反应失衡后引发大规模肝坏死”J Gastroenterol。

Kimura H, Mochida S, Inao M, et al.: "Angiopoietin/Tie Receptors System may Play a Role During Reconstruction and Capillarization of the Hepatic Sinusoids after Partial Hepatectomy and Liver Necrosis in Rats"Hepatol Res. (in press).

Kimura H、Mochida S、Inao M 等人：“血管生成素/领带受体系统可能在大鼠部分肝切除和肝坏死后肝窦的重建和毛细血管化过程中发挥作用”Hepatol Res。

Takahashi M, Matsui A, Inao M, et al.: "ERK/MAPK-Dependent PI3K/Akt Phosphorylation Through VEGFR-1 after VEGF Stimulation in Activated Hepatic Stellate Cells"Hepatol Res. 26. 232-236 (2003)

Takahashi M、Matsui A、Inao M 等人：“活化肝星状细胞中 VEGF 刺激后通过 VEGFR-1 进行 ERK/MAPK 依赖性 PI3K/Akt 磷酸化”Hepatol Res。