The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, State Key Laboratory of Dampness Syndrome of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510120, China; State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences Beijing, Research Unit of Proteomics & Research and Development of New Drug of Chinese Academy of Medical Sciences, Institute of Lifeomics, Beijing 102206, China.
State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences Beijing, Research Unit of Proteomics & Research and Development of New Drug of Chinese Academy of Medical Sciences, Institute of Lifeomics, Beijing 102206, China; Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Key Laboratory of Combinatorial Biosynthesis and Drug Discovery of Ministry of Education, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China.
Biochim Biophys Acta Gene Regul Mech. 2023 Jun;1866(2):194928. doi: 10.1016/j.bbagrm.2023.194928. Epub 2023 Mar 21.
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 CCl for only 3 days, which was significantly enhanced while given CCl 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 CCl 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.
肝纤维化的特征是肝组织中细胞外基质（ECM）的过度合成和沉积。然而，目前仍然缺乏早期检测和诊断方法。胶原杂交肽（CHP）是一种新型合成肽，能够检测胶原损伤和组织重塑。在这里，我们发现，给予 CCl 仅 3 天时，肝脏中就可以检测到明显的 CHP 阳性染色，而给予 CCl 7 天时则明显增强。然而，H&E 染色显示纤维组织没有明显变化，而天狼星红阳性染色仅在给予 CCl 14 天时才能观察到。此外，CHP 阳性染色最初在门脉区增强，进一步扩展到肝小叶，在 10 天和 14 天的模型中，其增加程度明显高于天狼星红阳性染色。对 CHP 阳性染色的蛋白质组学分析进一步表明，与 ECM 重塑相关的途径显著增加，而视黄醇代谢下调。同时，参与纤维化的细胞基因转录和信号转导相关的蛋白质也上调，提示 CHP 阳性染色发生了纤维化。我们的研究提供了证据表明，CHP 可以检测肝组织中的胶原损伤，这可能是肝纤维化早期诊断的有效指标。
