Human intrahepatic biliary epithelial cells proliferate in vitro in response to human hepatocyte growth factor.

Human intrahepatic biliary epithelial cells proliferate in vitro in response to human hepatocyte growth factor.
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人肝内胆管上皮细胞响应人肝细胞生长因子而在体外增殖。

DOI:
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发表时间:
1992
影响因子:
15.9
通讯作者:
A. Strain
A. Strain
中科院分区:
医学1区
文献类型:
--
作者:
R. Joplin;T. Hishida;H. Tsubouchi;Y. Daikuhara;Reuben Ayres;J. Neuberger;A. Strain

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在之前的研究中,分离出高纯度的肝内人胆管上皮细胞(BEC)。然而,这些细胞仅表现出有限的生长反应。在这里,我们报道人类 BEC 响应人类肝细胞生长因子 (hHGF) 进行增殖,保留 BEC 特异性表型,并且可以连续传代。 BEC 对 0.01-100 ng/ml hHGF 表现出剂量依赖性生长。在 1 ng/ml 的半最大刺激下,最大 S 期标记指数达到 40%。正常和原发性胆汁性肝硬化肝细胞对 hHGF 的反应相似。培养物用特异性抗体进行免疫染色,然后进行[3H]胸苷放射自显影。增殖细胞表达 BEC 特异性标记物(HEA125 和 CK-19),但结蛋白和因子 VIII 相关抗原呈阴性。偶尔观察到波形蛋白阳性细胞,但这些细胞是非增殖性的。总之,对 hHGF 做出反应的细胞显然起源于 BEC。 HGF 对 BEC 以及肝细胞具有促有丝分裂作用的观察结果具有重要意义。首先,肝内 BEC 的产量更高,可用于胆管上皮疾病的发病机制和病因学的后续研究。其次,体内调节细胞对 HGF 反应的一些方法必须发挥作用,因为 HGF 水平在部分肝切除术后早期就升高,但 BEC 比肝细胞晚 24 小时增殖。
In previous studies, intrahepatic human biliary epithelial cells (BEC) were isolated in high purity. However, these cells demonstrated only limited growth responses. Here we report that human BEC proliferate in response to human hepatocyte growth factor (hHGF), retain BEC-specific phenotype, and can be serially passaged. BEC showed dose-dependent growth in response to 0.01-100 ng/ml hHGF. The maximum S-phase labeling index reached 40% with half-maximal stimulation at 1 ng/ml. The response of cells from normal and primary biliary cirrhotic liver to hHGF was similar. Cultures were immunostained with specific antibodies and then processed for [3H]thymidine autoradiography. Proliferating cells expressed BEC-specific markers (HEA125 and CK-19), but were negative for desmin and factor VIII-related antigen. Occasional vimentin-positive cells were observed, but these were nonproliferative. In conclusion, cells responding to hHGF were clearly BEC in origin. The observation that HGF is mitogenic for BEC as well as hepatocytes has important implications. First, greater yields of intrahepatic BEC are available for subsequent studies of the pathogenesis and etiology of diseases of the biliary epithelium. Secondly, some means of regulating the cellular response to HGF in vivo must operate, in that HGF levels rise early after partial hepatectomy and yet BEC proliferate 24 h later than hepatocytes.
DOI: 10.1016/0006-291x(91)92020-k
发表时间: 1991-05
影响因子: 3.1
作者:
R. Zarnegar;M. Defrances;D. P. Kost;P. Lindroos;G. Michalopoulos
通讯作者: R. Zarnegar;M. Defrances;D. P. Kost;P. Lindroos;G. Michalopoulos
DOI: 10.1016/0003-2697(87)90673-7
发表时间: 1987-02-15
影响因子: 2.9
作者:
FRIEDMAN, SL;ROLL, FJ
通讯作者: ROLL, FJ
肝脏生长的调节:原癌基因和转化生长因子。
DOI: --
发表时间: 1989
期刊: Laboratory investigation; a journal of technical methods and pathology
影响因子: --
作者:
Fausto,N;Mead,JE
通讯作者: Mead,JE
DOI: 10.1159/000163564
发表时间: 1990
期刊: Pathobiology : journal of immunopathology, molecular and cellular biology
影响因子: --
作者:
A. Sirica;G. Mathis;N. Sano;L. Elmore
通讯作者: A. Sirica;G. Mathis;N. Sano;L. Elmore