Expression, localization and alternative splicing pattern of fibronectin messenger RNA in fibrotic human liver and hepatocellular carcinoma
Expression, localization and alternative splicing pattern of fibronectin messenger RNA in fibrotic human liver and hepatocellular carcinoma
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DOI：
10.1016/s0168-8278(97)80322-4
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发表时间：
1997-11-01
影响因子：
25.7
通讯作者：
Asakura, H
中科院分区：
文献类型：
--
作者：
Matsui, S;Takahashi, T;Asakura, H
背景/目的:纤维连接蛋白是一种多功能糖蛋白，在细胞与细胞或细胞与基质的相互作用中发挥重要作用。纤维连接蛋白的分子和功能多样性源于前mrna在三个可变区域（ED-A， ED-B和IIICS）的选择性剪接，具有ED-A和ED-B区域的细胞纤维连接蛋白与缺乏这些区域的血浆纤维连接蛋白具有不同的生物活性。本研究旨在探讨纤维连接蛋白在人类肝脏疾病中的类型特异性表达。方法：采用抗总纤维连接蛋白单克隆抗体和抗细胞纤维连接蛋白单克隆抗体免疫组化，用cDNA探针杂交检测常见区和ED-A区，RT-PCR扩增各可变区，其中对照组4例，慢性肝炎16例，肝硬化7例，肝癌8例。结果:对照组肝门静脉区有少量细胞性纤维连接蛋白[ED-A（+）纤维连接蛋白]沉积，慢性肝炎肝门静脉区纤维化扩大边缘有大量细胞性纤维连接蛋白沉积，肝硬化肝门静脉区纤维化间隔、肝癌肿瘤结节纤维间隔及包膜均有大量细胞性纤维连接蛋白沉积。细胞纤维连接蛋白mRNA定位于少数肝细胞和中央静脉周围的非实质细胞，随着肝纤维化的进展，纤维连接蛋白mRNA在纤维化扩大的门静脉区附近的相同细胞群中增加。在肝细胞癌中，它在大多数肝癌细胞中表达，RT-PCR在对照肝和各疾病组中检测到三个可变区域的纤维连接蛋白mRNA。结论：细胞纤维连接蛋白在人肝脏纤维化和肝癌中表达增加，在人肝脏中，非实质细胞和肝细胞共同参与细胞纤维连接蛋白的产生，在肝细胞癌中，肝癌细胞是主要的产生者，我们的结果表明，在人肝脏中，细胞纤维连接蛋白可能参与肝纤维化和肝细胞癌的恶性表型。
Background/Aims: Fibronectin is a multifunctional glycoprotein and plays important roles in cell-to-cell or cell-to-matrix interaction, The molecular and functional diversity of fibronectin arises from alternative splicing of pre-mRNA at three variable regions, termed ED-A, ED-B and IIICS, Cellular fibronectin with ED-A and ED-B regions has different biological activities from plasma fibronectin lacking these regions, This study was aimed at investigating the type-specific expression of fibronectin in human liver diseases.Methods: Immunohistochemistry with anti-total and anti-cellular fibronectin monoclonal antibodies, in sial hybridization with cDNA probes detecting common and ED-A regions and RT-PCR to amplify each variable region were performed in 35 specimens, including 4 control, 16 chronic hepatitis, 7 liver cirrhosis and 8 hepatocellular carcinoma.Results: In control liver, there were slight deposits of cellular fibronectin [ED-A(+)fibronectin] in portal areas, In chronic hepatitis, it was strongly deposited at the margin of the fibrously enlarged portal areas where new collagen fibers were formed, Cellular fibronectin was evenly and abundantly accumulated in fibrotic septa in liver cirrhosis, and in fibrotic septa and capsules of tumor nodules in hepatocellular carcinoma, In control liver, cellular fibronectin mRNA was localized in a few hepatocytes and non-parenchymal cells around central veins, and was increased in the same cell populations near fibrously enlarged portal areas as hepatic fibrosis progressed, In hepatocellular carcinoma, it was expressed in most hepatoma cells, Fibronectin mRNA with three variable regions was detectable by RT-PCR in control liver as well as in each disease group.Conclusions: The expression of cellular fibronectin was increased in fibrotic human liver and hepatocellular carcinoma, In human liver, both non-parenchymal cells and hepatocytes participated together in cellular fibronectin production, In hepatocellular carcinoma, hepatoma cells were the main producer, Our results indicate that, in human liver, cellular fibronectin may participate in the hepatic fibrogenesis and in the malignant phenotypes of hepatocellular carcinoma.