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自分泌骨桥蛋白参与多房棘球蚴的生长和转移。

Autocrine osteopontin is involved in maintaining the growth and metastasis of Echinococcus multilocularis.

机构信息

The First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, Xinjiang, China; School of Medicine, Shihezi University, Shihezi, Xinjiang, China.

The First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, Xinjiang, China.

出版信息

Acta Trop. 2022 Apr;228:106328. doi: 10.1016/j.actatropica.2022.106328. Epub 2022 Jan 24.

DOI:10.1016/j.actatropica.2022.106328
PMID:35085512
Abstract

Alveolar echinococcosis is a zoonotic disease that seriously endangers human health. This study aims to investigate the effects of osteopontin on the growth and intra- or extra-hepatic metastasis of Echinococcus multilocularis. Mice were randomly divided into untreated (control group, n = 25), PBS (n = 25), Lv3-NC (n = 25), and Lv-OPN-734 (n = 25) groups. Knockdown OPN by injecting lentivirus through the intraperitoneal portal vein, the metastatic lesions infected with Echinococcus multilocularis and adjacent liver tissues were observed, and the expression of osteopontin and epidermal growth factor receptor pathway-related molecules were studied. Gross observation of specimens suggested that there was no extra- hepatic metastasis, and mild intrahepatic invasion was observed in the Lv-OPN-734 group after 4 months of infection, and lung metastasis occurred in the Lv3-NC group. Western-blot and immunohistochemical staining results showed that the protein expression of OPN, phosphorylation of epidermal growth factor receptor and downstream molecules of the pathway decreased significantly after osteopontin knockdown, whereas the levels of non-phosphorylated proteins did not change significantly. In human tissues, through western-blot and immunohistochemical staining we found that compared with the control group, the expression of OPN in the liver tissues infected with Echinococcus multilocularis were higher than that in the control group. These findings indicate that osteopontin is involved in maintaining the growth and metastasis of Echinococcus multilocularis, suggesting that osteopontin may be a potential target for the treatment of alveolar echinococcosis.

摘要

泡球蚴病是一种严重危害人类健康的人畜共患寄生虫病。本研究旨在探讨骨桥蛋白(OPN)对泡球蚴生长及肝内、外转移的影响。将小鼠随机分为未处理组(对照组,n=25)、PBS 组(n=25)、Lv3-NC 组(n=25)和 Lv-OPN-734 组(n=25)。通过腹腔门静脉注射慢病毒敲低 OPN,观察感染泡球蚴的转移灶及邻近肝组织,研究骨桥蛋白和表皮生长因子受体通路相关分子的表达。大体标本观察提示无肝外转移,感染 4 个月后 Lv-OPN-734 组肝内见轻度侵犯,Lv3-NC 组出现肺转移。Western-blot 和免疫组化染色结果显示,骨桥蛋白敲低后 OPN 蛋白及其通路下游分子磷酸化表达显著降低,而非磷酸化蛋白水平无明显变化。在人组织中,通过 Western-blot 和免疫组化染色发现,与对照组相比,泡球蚴感染肝组织中 OPN 的表达高于对照组。这些发现表明骨桥蛋白参与泡球蚴的生长和转移,提示骨桥蛋白可能是治疗泡型包虫病的潜在靶点。

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