Wang Fang, Long Qi, Gong Yu, Hu Longbo, Zhang Hong, Oettgen Peter, Peng Tao
State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530 China.
State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530 China ; Max Planck Institute for Molecular Biomedicine, Röntgenstraße 20, 48149 Münster, Germany.
Cell Biosci. 2014 Dec 8;4(1):76. doi: 10.1186/2045-3701-4-76. eCollection 2014.
Golgi protein-73 (GP73) is a Golgi transmembrane glycoprotein elevated in numerous liver diseases. Clinically, GP73 is strongly elevated in the serum of HCC patients and is thus regarded as a novel potential biomarker for HCC. However, the mechanism leading to GP73 dysregulation in liver diseases remains unknown.
This study determined that epithelium-specific ETS (ESE)-1, an epithelium-specific transcription factor, and GP73 expressions were induced by IL-1β stimulation in vitro, and both were triggered during liver inflammation in vivo. In hepatocellular carcinoma cells, the overexpression of ESE-1 induced GP73 expression, whereas its knock-down did the opposite. Mechanistically, ESE-1 activated GP73 expression by directly binding to its promoter.
Our findings supported a novel paradigm for ESE-1 as a transcriptional mediator of GP73. This study provided a possible mechanism for GP73 upregulation in liver diseases.
高尔基体蛋白73（GP73）是一种在多种肝脏疾病中升高的高尔基体跨膜糖蛋白。临床上，GP73在肝癌患者血清中显著升高，因此被视为肝癌一种新的潜在生物标志物。然而，导致肝脏疾病中GP73失调的机制仍不清楚。
本研究确定，上皮特异性ETS（ESE）-1，一种上皮特异性转录因子，和GP73的表达在体外受白细胞介素-1β刺激诱导，且二者在体内肝脏炎症过程中均被触发。在肝癌细胞中，ESE-1的过表达诱导GP73表达，而其敲低则产生相反效果。机制上，ESE-1通过直接结合其启动子激活GP73表达。
我们的发现支持了ESE-1作为GP73转录调节因子的新范式。本研究为肝脏疾病中GP73上调提供了一种可能机制。
