Haemophilus parasuis induces severe acute systemic infection in pigs, characterized by fibrinous polyserositis, polyarthritis and meningitis. Our previous study demonstrated that H. parasuis induced the activation of p38 mitogen-activated protein kinase (MAPK) pathway, increasing the expression of proinflammatory genes and mediating H. parasuis-induced inflammation. Moreover, Wnt/β-catenin signaling activation induced by H. parasuis disrupts the adherens junction between epithelial cells and initiates the epithelial-mesenchymal transition (EMT). In the present study, p38 MAPK was found to be involved in the accumulation of nuclear location of β-catenin during H. parasuis infection in PK-15 and NPTr cells, via modulating the expression of dickkofp-1 (DKK-1), a negative regulator of Wnt/β-catenin signaling. We generated DKK-1 knockout cell lines by CRISPR/Cas9-mediated genome editing in PK-15 and NPTr cells, and found that knockout of DKK-1 led to the dysfunction of p38 MAPK in regulating Wnt/β-catenin signaling activity in H. parasuis-infected cells. Furthermore, p38 MAPK activity was independent of the activation of Wnt/β-catenin signaling during H. parasuis infection. This is the first study to explore the crosstalk between p38 MAPK and Wnt/β-catenin signaling during H. parasuis infection. It provides a more comprehensive view of intracellular signaling pathways during pathogenic bacteria-induced acute inflammation.

中文翻译：

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P38 丝裂原活化蛋白激酶通过阻止副猪嗜血杆菌感染期间 Dickkofp-1 的表达来促进 Wnt/β-catenin 信号传导

副猪嗜血杆菌在猪中引起严重的急性全身感染，其特征是纤维蛋白性多浆膜炎、多关节炎和脑膜炎。我们之前的研究表明，副猪嗜血菌诱导 p38 丝裂原活化蛋白激酶 (MAPK) 通路的激活，增加促炎基因的表达并介导副猪嗜血菌诱导的炎症。此外，副猪嗜血菌诱导的 Wnt/β-catenin 信号激活会破坏上皮细胞之间的粘附连接并启动上皮间质转化 (EMT)。在本研究中，发现 p38 MAPK 通过调节 dickkofp-1 (DKK-1) 的表达参与了副猪嗜血杆菌感染过程中 PK-15 和 NPTr 细胞中 β-catenin 核定位的积累。 Wnt/β-catenin 信号的负调节。我们在 PK-15 和 NPTr 细胞中通过 CRISPR/Cas9 介导的基因组编辑生成了 DKK-1 敲除细胞系，并发现敲除 DKK-1 导致 p38 MAPK 在调节 H 中 Wnt/β-catenin 信号活性方面的功能障碍。 . 副猪感染细胞。此外，p38 MAPK 活性与副猪嗜血菌感染期间 Wnt/β-catenin 信号传导的激活无关。这是第一项探索副猪嗜血菌感染期间 p38 MAPK 和 Wnt/β-catenin 信号传导之间的串扰的研究。它提供了病原菌引起的急性炎症期间细胞内信号通路的更全面的视图。p38 MAPK 活性与副猪嗜血杆菌感染期间 Wnt/β-catenin 信号传导的激活无关。这是第一项探索副猪嗜血菌感染期间 p38 MAPK 和 Wnt/β-catenin 信号传导之间的串扰的研究。它提供了病原菌引起的急性炎症期间细胞内信号通路的更全面的视图。p38 MAPK 活性与副猪嗜血杆菌感染期间 Wnt/β-catenin 信号传导的激活无关。这是第一项探索副猪嗜血菌感染期间 p38 MAPK 和 Wnt/β-catenin 信号传导之间的串扰的研究。它提供了病原菌引起的急性炎症期间细胞内信号通路的更全面的视图。