TRANSFORMING GROWTH-FACTOR-BETA-1 (TGF-BETA-1) AND TGF-BETA-1 RECEPTORS IN NORMAL, CIRRHOTIC, AND NEOPLASTIC HUMAN LIVERS
TRANSFORMING GROWTH-FACTOR-BETA-1 (TGF-BETA-1) AND TGF-BETA-1 RECEPTORS IN NORMAL, CIRRHOTIC, AND NEOPLASTIC HUMAN LIVERS
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DOI：
10.1002/hep.1840210325
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发表时间：
1995-03-01
期刊：
影响因子：
13.5
通讯作者：
POYNARD, T
中科院分区：
文献类型：
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作者：
BEDOSSA, P;PELTIER, E;POYNARD, T
转化生长因子-β1(TGF-β1)是控制肝细胞增殖和复制的重要介质。本研究的目的是比较正常肝脏、肝硬变结节和肿瘤人肝脏中转化生长因子-β1的基因表达、蛋白质合成和细胞膜受体。本研究采用原位杂交和免疫组织化学方法，检测了5例正常肝组织和25例肝细胞癌合并肝硬变患者肝组织中信使RNA和转化生长因子-β1蛋白的表达。用免疫组织化学方法检测组织切片中转化生长因子-β1 II型受体的表达。在正常肝组织中，转化生长因子-β1mRNA和蛋白均无显著表达。在肝硬变结节中，少数纤维间隔的窦状细胞和间充质细胞表达转化生长因子-β1mRNA。免疫组织化学染色显示，正常肝细胞和肝硬变肝细胞沿纤维间隔的细胞外基质中均有蛋白表达，而肿瘤性结节肝细胞胞浆中有较强的表达。尽管正常肝细胞胞膜上有转化生长因子-β1受体II的表达，但肿瘤肝细胞不再有膜标记，而是胞浆内弥漫性染色，并伴有核周聚集。这项研究表明，尽管肿瘤肝细胞过度表达转化生长因子-β1，但其逃脱了细胞增殖的控制，这可能与肝细胞膜上转化生长因子-β1受体II的加工缺陷有关。
Transforming growth factor-Beta 1 (TGF-beta 1) is an important mediator of control of Liver cell proliferation and replication. The aim of the current study was to compare TGF-beta 1 gene expression, protein synthesis, and cell membrane receptors in normal liver, cirrhotic nodules, and neoplastic human Livers. Five surgical resections for metastasis in an otherwise normal liver and 25 resections for hepatocellular carcinoma with cirrhosis were included in this study, Messenger RNA (mRNA) and TGF-beta 1 protein were detected on serial tissue sections of normal, cirrhotic, and tumoral livers using in situ hybridization and immunohistochemistry. TGF-beta 1 type II receptors were detected on tissue sections using immunohistochemistry. In normal Livers, TGF-beta 1 mRNA and protein were not significantly expressed. In cirrhotic nodules, a few sinusoidal cells and mesenchymal cells of fibrous septa displayed TGF-beta 1 mRNA. By immunohistochemistry, protein was detected in the extracellular matrix along the fibrous septa Hepatocytes from normal and cirrhotic livers did not express TGF-beta 1. In contrast, the cytoplasm Of hepatocytes in neoplastic nodules showed intense staining for TGF-beta 1 mRNA and protein. Although TGF-beta 1 receptor II was expressed on the plasma membrane of normal liver cells, tumoral hepatocytes no longer displayed membrane labeling but rather diffuse intracytoplasmic Staining with perinuclear accumulation. This study suggests that the escape of tumoral hepatocytes from control of cell proliferation by TGF-beta 1, despite its overexpression by these cells, might be related to a defect in TGF-beta 1 receptor II processing on the liver cell membrane.