Expression of the stem cell factor receptor c-kit in normal and diseased pediatric liver:: Identification of a human hepatic progenitor cell?
Expression of the stem cell factor receptor c-kit in normal and diseased pediatric liver:: Identification of a human hepatic progenitor cell?
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DOI：
10.1002/hep.510300140
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发表时间：
1999-07-01
期刊：
影响因子：
13.5
通讯作者：
Strain, AJ
中科院分区：
文献类型：
--
作者：
Baumann, U;Crosby, HA;Strain, AJ
干细胞因子（SCF）/c-kit配体/受体系统与大鼠肝损伤后的干（卵圆）细胞活化有关。本研究的目的是确定SCF/c-kit系统在儿童急性和慢性肝损伤中的作用。取因肝外胆道闭锁（EHBA）和暴发性肝功能衰竭（FHF）而接受肝移植的患者的肝切除标本，用核糖核酸酶保护法和免疫组织化学法测定组织切片中c-kit和β-actin的特异性表达。c-kit的表达在正常和肝硬化（EHBA）中检测到相对一致的水平。然而，在FHF中，c-hit mRNA水平在6个标本中的3个中升高。免疫定位突出了在正常肝脏的汇管区中存在少量的c-hit阳性细胞，而在异位肝脏中数量增加。然而，在FHF中观察到最高的c-hit染色，其中除了汇管区中的细胞外，还发现离散的c-hit阳性细胞整合到胆管中。共定位研究表明，一些c-kit阳性细胞是肥大细胞，白细胞和造血细胞的起源。然而，仍有一个子集对这些标记物也呈阴性。c-hit受体在病变肝脏中的表达上调表明该受体/配体系统参与了肝脏修复机制，我们推测c-hit阳性细胞可能代表了肝脏祖细胞群。这些c-hit阳性细胞的起源和生长/分化潜力正在研究中。
The stem cell factor (SCF)/c-kit ligand/receptor system has been implicated in stem (oval) cell activation following liver injury in the rat. The aim of this study was to determine the role of the SCF/c-kit system in pediatric human liver during acute and chronic liver injury. Tissue was obtained from hepatectomy specimens of patients undergoing liver transplantation for extrahepatic biliary atresia (EHBA) and fulminant hepatic failure (FHF), Specific expression of mRNA for c-hit and beta-actin was measured by ribonuclease protection and by immunohistochemistry to localize c-kit in tissue sections. Expression of c-kit was detected at relatively consistent levels in normal and cirrhotic (EHBA) livers. However, in FHF, c-hit mRNA levels were elevated in 3 of 6 specimens. Immunolocalization highlighted the presence of small numbers of c-hit-positive cells in the portal tracts of normal livers with increased numbers in cirrhotic livers. The highest c-hit staining, however, was observed in FHF, in which, in addition to the cells in the portal tracts, discrete c-hit-positive cells were also found integrated into bile ducts. Colocalization studies demonstrated some of the c-kit-positive cells to be of mast cell, leukocyte, and hematopoietic cell origin. However, there remained a subset that was also negative for these markers. The up-regulation of c-hit receptor expression in diseased livers suggests an involvement of this receptor/ ligand system in hepatic repair mechanisms, and we speculate that c-hit-positive cells may represent a hepatic progenitor cell population. The origin and growth/differentiation potential of these c-hit-positive cells is under investigation.