Localization of liver myofibroblasts and hepatic stellate cells in normal and diseased rat livers: distinct roles of (myo-)fibroblast subpopulations in hepatic tissue repair
Localization of liver myofibroblasts and hepatic stellate cells in normal and diseased rat livers: distinct roles of (myo-)fibroblast subpopulations in hepatic tissue repair
复制标题
DOI：
10.1007/s004180050421
复制
发表时间：
1999-11-01
影响因子：
2.3
通讯作者：
Ramadori, G
中科院分区：
文献类型：
--
作者：
Knittel, T;Kobold, D;Ramadori, G
以往的体外研究表明，肝星状细胞(HSC)和大鼠肝脏肌成纤维细胞(RMF)是肌成纤维细胞系中具有纤维化潜能的不同细胞群。利用这些研究定义的区别性特征，分析了HSC和RMF在病变肝脏中的定位。用免疫组织化学和原位杂交法对正常肝、急性肝损伤和慢性肝损伤进行分析。在正常肝组织中，结蛋白/胶质纤维酸性蛋白(GFAP)阳性细胞分布于肝实质，而RMF(结蛋白/平滑肌α-肌动蛋白阳性，GFAP阴性细胞与纤维蛋白-2共存)分布于汇管区、中央静脉壁，仅偶见于肝实质。急性肝损伤的特征几乎完全是HSC数量的增加，而RMF的数量几乎没有变化。在纤维化的早期阶段，在发展中的瘢痕内可检测到HSC和RMF。在纤维化晚期，HSC主要位于瘢痕-实质交界处，而RMF占大部分位于瘢痕内的细胞。在肝纤维化的每一阶段，与HSC相反，RMF仅偶尔在肝实质中检测到。HSC和RMF存在于正常和病变的肝脏中，存在于不同的间隔，对组织损伤的反应不同。在急性肝损伤之后，HSC的数量几乎完全增加，而在慢性损伤的肝脏中，不仅HSC，而且RMF参与了瘢痕的形成。
Previous in vitro studies indicated that hepatic stellate cells (HSC) and rat liver myofibroblasts (rMF) have to be regarded as different cell populations of the myofibroblastic lineage with fibrogenic potential. Employing the discrimination features defined by these studies the localization of HSC and rMF was analyzed in diseased livers. Normal and acutely as well as chronically carbon tetrachloride-injured livers were analyzed by immunohistochemistry and by in situ hybridization. In normal livers HSC [desmin/glial fibrillary acid protein (GFAP)-positive cells] were distributed in the hepatic parenchyma, while rMF (desmin/smooth muscle alpha actin-positive, GFAP-negative cells colocalized with fibulin-2) were located in the portal field, the walls of central veins, and only occasionally in the parenchyma. Acute liver injury was characterized almost exclusively by an increase in the number of HSC, while the amount of rMF was nearly unchanged. In early stages of fibrosis, HSC and rMF were detected within the developing scars. In advanced stages of fibrosis, HSC were mainly present at the scar-parenchymal interface, while rMF accounted for the majority of the cells located within the scar. At every stage of fibrogenesis, rMF, in contrast to HSC, were only occasionally detected in the hepatic parenchyma. HSC and rMF are present in normal and diseased livers in distinct compartments and respond differentially to tissue injury. Acute liver injury is followed by an almost exclusive increase in the number of HSC, while in chronically injured livers not only HSC but also rMF are involved in scar formation.