A role of extracellular matraix on regeneration of the liver : Involvement of sinusoidal endothelial cell growth factors.

细胞外基质对肝脏再生的作用：肝窦内皮细胞生长因子的参与。

基本信息

批准号：
62570327
负责人：
KOIDE Norio
金额：
$ 1.09万
依托单位：
Okayama University Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1988
项目状态：
已结题

项目摘要

It was known that many factors are involved in the regeneration and tissue repair of the liver. The involvement of extracellular matrix, especially reticulin fibers in Disse's space of the liver as well as the interaction between hapatocyates and sinusoidal endothelial cells, in these mechanism was considered to be one of important factors. By the support of previous Grant-in-Aid for Scientific Research (C); 5857032, we have found that the reticulin fibers were composed of collagens, glycoproteins and proteoglycans and developed to utilize each component as a culture substrate in the primary culture of adult rat hepatocytes. By the support of the present Grant-in Aid for Scientific Research (C) we found that 1) adult rat hepatocyates assembled to various forms specific to each component; 2) hepatocytes formed multicellular spheroid in responce to the solid state of proteoglycans used as asubstrate; 3) hepatocyates in the multicelluar spheroid exhibited morphologically defined differentiated structures and biochemically defined differentiated functions, and did poor proliferative abiliaty; 4) the multicallular spheroids were not only formed with hepatocytes but also with a mixture of heterotypic cells, hepatocyates and sinusoidal endotahelial cells; 5) since numerous bile canaliculi-like structures and Golji complexes were observed only in the heterotypic cells-spheroids, the level of tissue organization was raised to an upper level in the heterotypic cells-spheroid than the hepatocytes-spheroid; 6) fresh rat serum contained high molecular weight glycoproteins that induced the proliferation of sinusoidal endothelial cells of rat liver.

众所周知，肝脏的再生和组织修复涉及许多因素。细胞外基质，特别是肝迪斯间隙中网状纤维的参与以及肝细胞与肝窦内皮细胞之间的相互作用被认为是该机制中的重要因素之一。受到先前科学研究资助金的支持（C）；在美国专利号5857032中，我们发现网状纤维由胶原蛋白、糖蛋白和蛋白聚糖组成，并开发利用每种成分作为成年大鼠肝细胞原代培养中的培养基质。在目前的科学研究资助（C）的支持下，我们发现1）成年大鼠肝细胞中的每个成分都组装成各种特定的形式； 2)肝细胞响应于用作底物的固态蛋白多糖而形成多细胞球体； 3)多细胞球体中的肝细胞酸盐表现出形态学上明确的分化结构和生化上明确的分化功能，并且增殖能力差； 4)多胼胝体球体不仅由肝细胞形成，而且由异型细胞、肝细胞和肝窦内皮细胞的混合物形成； 5)由于仅在异型细胞球体中观察到大量胆小管样结构和Golji复合体，因此异型细胞球体中的组织组织水平比肝细胞球体提高到较高水平； 6)新鲜大鼠血清中含有高分子量糖蛋白，可诱导大鼠肝窦内皮细胞增殖。