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曼氏血吸虫卵诱导 Wnt/β-连环蛋白信号通路并激活人及仓鼠结肠原癌基因 c-Jun。

Schistosoma mansoni eggs induce Wnt/β-catenin signaling and activate the protooncogene c-Jun in human and hamster colon.

机构信息

Department of Gastroenterology, Justus Liebig University, Gaffkystr. 11, 35392, Giessen, Germany.

Institute of Parasitology, BFS, Justus Liebig University, Giessen, Germany.

出版信息

Sci Rep. 2020 Dec 23;10(1):22373. doi: 10.1038/s41598-020-79450-4.

Abstract

Schistosomiasis (bilharzia) is a neglected tropical disease caused by parasitic flatworms of the genus Schistosoma, with considerable morbidity in parts of the Middle East, South America, Southeast Asia, in sub-Saharan Africa, and particularly also in Europe. The WHO describes an increasing global health burden with more than 290 million people threatened by the disease and a potential to spread into regions with temperate climates like Corsica, France. The aim of our study was to investigate the influence of S. mansoni infection on colorectal carcinogenic signaling pathways in vivo and in vitro. S. mansoni infection, soluble egg antigens (SEA) and the Interleukin-4-inducing principle from S. mansoni eggs induce Wnt/β-catenin signaling and the protooncogene c-Jun as well as downstream factor Cyclin D1 and markers for DNA-damage, such as Parp1 and γH2a.x in enterocytes. The presence of these characteristic hallmarks of colorectal carcinogenesis was confirmed in colon biopsies from S. mansoni-infected patients demonstrating the clinical relevance of our findings. For the first time it was shown that S. mansoni SEA may be involved in the induction of colorectal carcinoma-associated signaling pathways.

摘要

血吸虫病(裂体吸虫病)是一种由血吸虫属寄生虫引起的被忽视的热带病,在中东、南美洲、东南亚、撒哈拉以南非洲的部分地区以及特别是在欧洲,该病发病率相当高。世界卫生组织描述了一种日益严重的全球健康负担,全球有超过 2.9 亿人受到这种疾病的威胁,而且这种疾病有可能传播到像法国科西嘉岛这样的温带地区。我们的研究目的是调查曼氏血吸虫感染对体内和体外结直肠致癌信号通路的影响。曼氏血吸虫感染、可溶性虫卵抗原(SEA)和曼氏血吸虫卵中的白细胞介素 4 诱导原诱导 Wnt/β-catenin 信号通路以及原癌基因 c-Jun 以及下游因子细胞周期蛋白 D1 和 DNA 损伤标志物,如 Parp1 和 γH2a.x 在肠细胞中。从曼氏血吸虫感染患者的结肠活检中证实了这些结直肠癌变特征性标志的存在,证明了我们研究结果的临床相关性。首次表明,曼氏血吸虫 SEA 可能参与诱导与结直肠癌相关的信号通路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e78b/7758332/bc6ef031e168/41598_2020_79450_Fig1_HTML.jpg

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