胶原杂交肽检测损伤胶原作为早期肝纤维化的有效诊断指标

IF 2.6 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Ping Tao , Jinfang Liu , Yuan Li , Tao Zhang , Fangzhou Wang , Lei Chang , Chonghui Li , Xinlan Ge , Tao Zuo , Shichun Lu , Yuanyuan Ruan , Zhimin Yang , Ping Xu
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引用次数: 1

摘要

肝纤维化的特点是肝组织中细胞外基质(ECM)的过度合成和沉积。然而,目前仍缺乏早期发现和诊断方法。胶原杂交肽(collagen hybridizing peptide, CHP)是一种用于检测胶原损伤和组织重塑的新型合成肽。在这里,我们发现CCl4仅给药3天,肝脏中可以检测到明显的chp阳性染色,而CCl4给药7天,chp阳性染色明显增强。但H&E染色未见纤维组织明显变化,天狼星红阳性染色仅在给予CCl4 14天后出现。chp阳性染色在门静脉区开始增强,并进一步向肝小叶延伸,在第10和14天的模型中,chp阳性染色比天狼星红阳性染色明显增加。chp阳性染色的进一步蛋白质组学分析显示,与ECM重塑相关的通路显著增加,而视黄醇代谢下调。同时,参与纤维形成的细胞基因转录和信号转导富集蛋白也上调,提示chp阳性染色发生了纤维化。我们的研究证明CHP可以检测到肝脏的胶原损伤,这可能是早期诊断肝纤维化的有效指标。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Damaged collagen detected by collagen hybridizing peptide as efficient diagnosis marker for early hepatic fibrosis

Liver fibrosis is characterized by excessive synthesis and deposition of extracellular matrix (ECM) in liver tissues. However, it still has been lacking of early detection and diagnosis methods. The collagen hybridizing peptide (CHP) is a novel synthetic peptide that enables detection of collagen damage and tissue remodeling. Here, we showed that obvious CHP-positive staining could be detected in the liver while given CCl4 for only 3 days, which was significantly enhanced while given CCl4 for 7 days. However, H&E staining showed no significant changes in fibrous tissue, and sirius red-positive staining could only be observed while given CCl4 for 14 days. Moreover, CHP-positive staining enhanced initially at portal area which further extended into the hepatic lobule, which was increased more significantly than sirius red-positive staining in the model of 10 and 14 days. Further proteomic analysis of CHP-positive staining revealed that pathways associated with ECM remodeling were significantly increased, while retinol metabolism was downregulated. Meanwhile, proteins enriched in cellular gene transcription and signal transduction involved in fibrogenesis were also upregulated, suggesting that fibrosis occurred in CHP-positive staining. Our study provided evidence that CHP could detect the collagen damage in liver, which might be an efficient indicator for the diagnosis of liver fibrosis at a very early stage.

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来源期刊
CiteScore
9.20
自引率
2.10%
发文量
63
审稿时长
44 days
期刊介绍: BBA Gene Regulatory Mechanisms includes reports that describe novel insights into mechanisms of transcriptional, post-transcriptional and translational gene regulation. Special emphasis is placed on papers that identify epigenetic mechanisms of gene regulation, including chromatin, modification, and remodeling. This section also encompasses mechanistic studies of regulatory proteins and protein complexes; regulatory or mechanistic aspects of RNA processing; regulation of expression by small RNAs; genomic analysis of gene expression patterns; and modeling of gene regulatory pathways. Papers describing gene promoters, enhancers, silencers or other regulatory DNA regions must incorporate significant functions studies.
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