Alteration of protein glycosylation in human hepatic stellate cells activated with transforming growth factor-β1
Alteration of protein glycosylation in human hepatic stellate cells activated with transforming growth factor-β1
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DOI：
10.1016/j.jprot.2012.05.040
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发表时间：
2012-07-16
影响因子：
3.3
通讯作者：
Li, Zheng
中科院分区：
文献类型：
--
作者：
Qin, Yannan;Zhong, Yaogang;Li, Zheng
尽管人糖蛋白糖基化异常与肝纤维化有关，肝纤维化是由肝星状细胞(HSCs)激活引起的慢性肝损伤所致，但与转化生长因子-β1(TGF-β1)激活HSCs有关的蛋白糖基化的精确变化却知之甚少。用转化生长因子-β1激活人肝星状细胞LX-2，用凝集素芯片检测活化的肝星状细胞与静止的肝星状细胞相比蛋白质糖基化的变化。用凝集素组织化学进一步验证凝集素结合图谱，并评估细胞内糖苷残基的分布。结果表明，与静止状态的LX-2相比，激活的LX-2中有14种凝集素(如AAL、PHA-E、ECA和ConA)信号增强，而7种凝集素(如UEA-I和GNA)信号减弱。同时，AAL、PHA-E和ECA染色显示静止的LX-2与细胞膜呈中度结合，而在激活的LX-2的相同区域结合增强。综上所述，与HSC激活相关的蛋白糖基化的精确变化可能为寻找HSC激活的新的分子机制和抗纤维化治疗策略提供有用的信息。(C)2012爱思唯尔B.V.保留所有权利。
Although aberrant glycosylation of human glycoproteins is related to liver fibrosis that results from chronic damage to the liver in conjunction with the activation of hepatic stellate cells (HSCs), little is known about the precision alteration of protein glycosylation referred to the activation of HSCs by transforming growth factor-beta 1 (TGF-beta 1). The human HSCs, LX-2 were activated by TGF-beta 1. The lectin microarrays were used to probe the alteration of protein glycosylation in the activated HSCs compared with the quiescent HSCs. Lectin histochemistry was used to further validate the lectin binding profiles and assess the distribution of glycosidic residues in cells. As a result, 14 lectins (e. g. AAL, PHA-E, ECA and ConA) showed increased signal while 7 lectins (e. g. UEA-I and GNA) showed decreased signal in the activated LX-2 compared with the quiescent LX-2. Meanwhile, AAL, PHA-E and ECA staining showed moderate binding to the cytoplasma membrane in the quiescent LX-2, and the binding intensified in the same regions of the activated LX-2. In conclusion, the precision alteration of protein glycosylation related to the activation of the HSCs may provide useful information to find new molecular mechanism of HSC activation and antifibrotic therapeutic strategies. (c) 2012 Elsevier B.V. All rights reserved.