Expression of reelin in hepatic stellate cells and during hepatic tissue repair: a novel marker for the differentiation of HSC from other liver myofibroblasts

Expression of reelin in hepatic stellate cells and during hepatic tissue repair: a novel marker for the differentiation of HSC from other liver myofibroblasts
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DOI:
10.1016/s0168-8278(02)00050-8
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发表时间:
2002-05-01
影响因子:
25.7
通讯作者:
Knittel, T
Knittel, T
中科院分区:
医学1区
文献类型:
--
作者:
Kobold, D;Grundmann, A;Knittel, T

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背景/目标:肝星状细胞(HSC)和大鼠肝肌成纤维细胞(rMF)是两个相似但不完全相同的细胞群,在肝组织修复过程中起着重要作用。方法:采用m-RNA-profiling技术,从HSC和rMF制备c-DNA,鉴定不同成纤维细胞群的标志蛋白。通过其在HSC中的存在和在rMF衍生的样品中的不存在来鉴定细胞外基质蛋白reelin。通过北方印迹分析和免疫沉淀证实,在静息和活化的HSC中存在类似量的reelin表达,并且在rMF中检测不到。因此,reelin是目前唯一可用于区分处于任何分化阶段的HSC与rMF的标志物。在一个单一的四氯化碳介导的肝损伤,reelin特异性mRNA诱导早期,升高到24小时后,四氯化碳剂量和减少之后。位于损伤区域的肝细胞和非实质肝细胞被确定为增强的reelin表达的主要细胞来源。虽然reelin表达上调肝损伤过程中,reelin缺陷小鼠完全恢复,这表明在组织修复反应或冗余的情况下,通过相关蛋白质的作用更明显的作用。(C)2002年欧洲肝脏研究协会。由Elsevier Science B. V.出版,版权所有。
Background/Aims: Hepatic stellate cells (HSC) and rat liver myofibroblasts (rMF), two similar but not identical cell populations, play a major role during hepatic tissue repair.Methods: To identify marker proteins for the different fibroblastic cell populations, m-RNA-profiling technology was employed using c-DNAs prepared from HSC and rMF.Results/Conclusions: The extracellular matrix protein reelin was identified through its presence in HSC and absence in rMF derived samples. As confirmed by Northern blot analysis and by immunoprecipitation, reelin expression was present in similar amounts in resting and activated HSC and was not detectable in rMF. Therefore reelin is the only marker presently available to distinguish HSC at any stage of differentiation from rMF. Following a single CCl4 mediated liver injury, reelin specific mRNAs were induced early, were elevated up to 24 h following CCl4 dosage and were diminished afterwards. Hepatocytes and non-parenchymal liver cells located in the damaged areas were identified as the main cellular source of enhanced reelin expression. Although reelin expression was upregulated during liver injury, reelin deficient mice recovered completely suggesting either a more distinct role in tissue repair reactions or a case of redundancy through the action of related proteins. (C) 2002 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.