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感染期间参与胆管纤维化的锯齿状蛋白-1/Notch信号通路及关键瞬时标志物

Jagged-1/Notch Pathway and Key Transient Markers Involved in Biliary Fibrosis during Infection.

作者信息

Kovner Anna, Zaparina Oxana, Kapushchak Yaroslav, Minkova Galina, Mordvinov Viatcheslav, Pakharukova Maria

机构信息

Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, Russia.

Institute of Molecular Biology and Biophysics, Subdivision of FRC FTM, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630117, Russia.

出版信息

Trop Med Infect Dis. 2022 Nov 9;7(11):364. doi: 10.3390/tropicalmed7110364.

Abstract

Chronic opisthorchiasis associated with infection is accompanied by severe fibrotic complications. It is of high practical significance to elucidate the mechanisms of hepatic fibrosis in chronic infection dynamics. The goal of the study is to investigate the temporal profile of key markers and the Jagged1/Notch signaling pathway in the implementation of fibrosis in a chronic infection. For the first time, using histological methods and real-time PCR analysis, we demonstrated the activation of the Jagged1/Notch pathway in liver fibrogenesis, including the activation of the and target genes during experimental opisthorchiasis in . Cluster analysis followed by regression analysis of key markers during the infection showed that Jagged1 and Mmp9have the greatest contribution to the development of cholangiofibrosis and periductal fibrosis. Moreover, we detected a significant increase in the number of Jagged1-positive cells in the liver of chronic opisthorchiasis patients compared to that of the control group without infection. The results of the study are extremely informative both in terms of investigation both diverse fibrosis mechanisms as well as potential targets in complex antihelmintic therapy.

摘要

与感染相关的慢性华支睾吸虫病伴有严重的纤维化并发症。阐明慢性感染动态过程中肝纤维化的机制具有很高的实际意义。本研究的目的是调查关键标志物的时间变化情况以及Jagged1/Notch信号通路在慢性感染导致纤维化过程中的作用。我们首次使用组织学方法和实时PCR分析,证明了Jagged1/Notch通路在肝纤维化形成过程中的激活,包括在实验性华支睾吸虫病期间小鼠中该通路及靶基因的激活。对感染期间关键标志物进行聚类分析并随后进行回归分析,结果显示Jagged1和Mmp9对胆管纤维化和导管周围纤维化的发展贡献最大。此外,我们检测到与未感染的对照组相比,慢性华支睾吸虫病患者肝脏中Jagged1阳性细胞数量显著增加。本研究结果在研究多种纤维化机制以及抗蠕虫综合治疗的潜在靶点方面都极具参考价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3de1/9697314/37b862760e44/tropicalmed-07-00364-g001.jpg

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