INCREASED TRANSFORMING GROWTH FACTOR-BETA-1 GENE-EXPRESSION IN HUMAN LIVER-DISEASE
INCREASED TRANSFORMING GROWTH FACTOR-BETA-1 GENE-EXPRESSION IN HUMAN LIVER-DISEASE
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DOI：
10.1016/0168-8278(92)90168-o
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发表时间：
1992-03-01
影响因子：
25.7
通讯作者：
ZERN, MA
中科院分区：
文献类型：
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作者：
ANNONI, G;WEINER, FR;ZERN, MA
我们最近证实了转化生长因子-β1在体外刺激肝细胞胶原合成，并且在两种肝纤维化模型中，该细胞因子的合成明显增加。在本研究中，我们研究了转化生长因子-β1(TFG-β-1)基因表达与人类肝病的关系。对16例活动性肝病患者进行了经皮肝穿活检以进行诊断。从每个活检组织的未使用部分提取总RNA，然后与下列人类cDNA克隆进行杂交分析：白蛋白、前-α-1(I)胶原和转化生长因子-β-1。以2例非肝病患者的手术肝活检标本作为对照。与对照组相比，活动性肝病患者的白蛋白降低了19%，I型胶原增加了97%，转化生长因子-β1mRNA水平增加了120%。此外，稳态水平的转化生长因子-β-1和前胶原蛋白mRNAs显著相关。核连续分析显示，两名纤维化患者的肝脏中的转化生长因子-β-1转录速率比对照肝脏的转录速率高2倍以上。这些发现表明，在活动性肝病期间，人类转化生长因子-β1基因的表达显著增强。
We recently demonstrated that transforming growth factor-beta-1 stimulates collagen synthesis in hepatic cells in vitro, and that the synthesis of this cytokine is markedly increased in two rodent models of hepatic fibrosis. In the present study, we investigated the association of transforming growth factor-beta-1 (TFG-beta-1) gene expression in human liver disease. Sixteen patients with active liver disease had percutaneous liver biopsies performed for diagnostic purposes. Total RNA was extracted from an unused portion of each biopsy and then subjected to hybridization analysis with the following human cDNA clones: albumin, pro-alpha-1 (I) collagen, and TGF-beta-1. Surgical liver biopsy specimens from two patients without hepatic disease were used as controls. When compared to controls, the patients with active liver disease had a 19% decrease in albumin, a 97% increase in type I collagen, and a 120% increase in transforming growth factor-beta-1 mRNA levels. Moreover, steady-state levels of TGF-beta-1 and procollagen mRNAs were significantly correlated. Nuclear run-on assays showed that livers from two patients with fibrosis had TGF-beta-1 transcription rates that were more than 2-fold higher than rates in control livers. These findings indicate that transforming growth factor-beta-1 gene expression is significantly enhanced in man during active liver disease.