Thy-1 is expressed in myofibroblasts but not found in hepatic stellate cells following liver injury

Thy-1 is expressed in myofibroblasts but not found in hepatic stellate cells following liver injury
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DOI:
10.1007/s00418-008-0503-y
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发表时间:
2009-01-01
影响因子:
2.3
通讯作者:
Ramadori, Giuliano
Ramadori, Giuliano
中科院分区:
生物学3区
文献类型:
--
作者:
Dudas, Jozsef;Mansuroglu, Tumen;Ramadori, Giuliano

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Thy-1(CD 90)是在与伤口愈合和纤维化相关的成纤维细胞群中诱导的粘附分子。在这项研究中,是否可以诱导肝星状细胞(HSC)在体内,在肝损伤或肝再生的条件下,Thy-1基因的表达的问题得到解决。用四氯化碳(CCl 4)诱导大鼠急性和慢性肝损伤。为了进行比较,还研究了人肝移植和大鼠67%部分肝切除术(PH)。Thy-1基因表达也在分离的人肝肌成纤维细胞中进行了检测。Thy-1-mRNA表达在慢性肝损伤中显著上调。Thy-1(+)细胞在正常、损伤和再生状态下的大鼠肝标本门静脉周围区均有表达。在慢性人类和大鼠肝损伤中,Thy-1(+)细胞主要位于瘢痕组织中。在CCl 4处理后的中央周围坏死区,没有发现Thy-1的诱导。Gremlin和Thy-1在门静脉周围区域显示出相似的定位。Thy-1在正常或毛细血管化的血窦中均未检测到,在分离的大鼠HSC中,既不能被分离的HSC中的炎性细胞因子诱导,也不能在治疗的肌成纤维细胞中上调。基于这些数据,Thy-1不是“活化的”正弦HSC的标志物,但它是在汇管区和瘢痕组织中发现的“活化的”(肌)成纤维细胞的标志物。
Thy-1 (CD90) is an adhesion molecule induced in fibroblast populations associated with wound healing and fibrosis. In this study the question whether Thy-1-gene-expression can be induced in hepatic stellate cells (HSC) in vivo, under conditions of liver injury or liver regeneration was addressed. Acute and chronic rat liver injury was induced by the administration of CCl4. For comparison, cirrhotic human liver, and rat 67% partial hepatectomy (PH) was studied as well. Thy-1-gene-expression was examined also in isolated human liver myofibroblasts. Thy-1-mRNA expression was significantly upregulated in chronic liver injury. Thy-1(+) cells were detected in the periportal area of rat liver specimens in normal-, injured- and regenerative-conditions. In chronic human and rat liver injury, Thy-1(+) cells were located predominantly in scar tissue. In the pericentral necrotic zone after CCl4-treatment, no induction of Thy-1 was found. Gremlin and Thy-1 showed comparable localization in the periportal areas. Thy-1 was not detected in either normal or capillarized sinusoids, in isolated rat HSC, and was neither inducible by inflammatory cytokines in isolated HSC, nor upregulated in treated myofibroblasts. Based upon these data Thy-1 is not a marker of "activated" sinusoidal HSC, but it is a marker of "activated" (myo)fibroblasts found in portal areas and in scar tissue.