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Carcinogenesis and Ito cell

癌变与伊藤细胞

基本信息

批准号：
08670598
负责人：
SAKAIDA Isao
金额：
$ 1.41万
依托单位：
Yamaguchi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670598/
关键词：
Ito cell Cancer Fibrosis Preneoplastic lesion TGF-beta1 肝発癌発癌

项目摘要

Administration of a choline deficient L-amino acid defined (CDAA) diet for 16 weeks led to the development of preneoplastic lesions that were positive for the placental form of glutathione S-transferase (GSTP) and induced hepatocellular carcinoma in 90% of rats after one year. Prolyl 4-hydroxylase inhibitor (HOE 077, 200 ppm) significantly reduced the size and incidence of preneoplastic lesions after 16 weeks and also the incidence of HCC (50%) in rats fed a CDAA diet for one year by the inactivation of Ito cell resulting in the prevention of fibrosis.Injection of pig serum into rats twice a week for 8 weeks induced.TGF-beta_1 mRNA expression and protein production resulting in liver fibrosis without parenchymal cell injury. Administration of a choline deficient L-amino acid defined (CDAA) diet for 6 weeks with or without pig serum pretreatment led to the development of preneoplastic lesions that were positive for the placental form of glutathione S- transferase (GSTP). Pig serum pretreatment induced more activated stellate cells with increased TGF-beta_1, mRNA expression and protein production in the livers of rats subsequently fed a CDAA diet for 6 weeks compared to rats fed the CDAA diet alone.These results indicate that pre-existing fibrosis with the activated stellate cells accelerates the development of preneoplastic lesions in a CDAA.diet model and that TGF-beta_1 induced by pig serum treatment failed to prevent the development of preneoplastic lesions in a CDAA-diet model.Cancer cell seems to prevent the activation of Ito cell in co-culture system but further examinations are necessary.

以胆碱缺乏的L氨基酸饲料喂养大鼠16周，可引起胎盘型谷胱甘肽S转移酶阳性的癌前病变，1年后90%的大鼠发生肝细胞癌。Prolyl 4-羟基酶抑制剂(HOE 077,200ppm)可通过使Ito细胞失活，预防肝纤维化，显著减少16周后癌前病变的大小和发生率，并降低肝细胞癌(50%)的发生率。大鼠每周两次注射猪血清，连续8周，转化生长因子-β1mRNA和蛋白的表达和蛋白产生导致肝纤维化，而实质细胞没有损伤。给予胆碱缺乏的L氨基酸限定饮食6周，并加或不加猪血清预处理，可导致胎盘型谷胱甘肽S转移酶阳性的癌前病变的发生。与单纯饲喂CDAA饲料的大鼠相比，猪血清预处理诱导了更多的活化星状细胞，并增加了肝组织中转化生长因子-β1的表达和蛋白产量。这些结果表明，在CDAA饮食模型中，活化的星状细胞预先存在的纤维化加速了癌前病变的发展，而猪血清处理诱导的转化生长因子-β1在CDAA饮食模型中未能阻止癌前病变的发展。在共培养系统中，癌细胞似乎阻止了Ito细胞的激活，但需要进一步的检查。