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酵母和菌丝阶段通过不同的信号通路诱导牛乳腺上皮细胞凋亡。

The Yeast and Hypha Phases of Induce the Apoptosis of Bovine Mammary Epithelial Cells via Distinct Signaling Pathways.

作者信息

Miao Yuhang, Ding Tao, Liu Yang, Zhou Xuezhang, Du Jun

机构信息

College of Life Science, Ningxia University, Yinchuan 750021, China.

Key Laboratory of the Ministry of Education for the Conservation and Utilization of Special Biological Resources of Western China, Ningxia University, Yinchuan 750021, China.

出版信息

Animals (Basel). 2023 Oct 15;13(20):3222. doi: 10.3390/ani13203222.

Abstract

Infection with spp. is a significant cause of bovine mastitis globally. We previously found that was the main pathogen causing mycotic mastitis in dairy cows in Yinchuan, Ningxia, China. However, whether the infection of this pathogen could induce apoptosis in BMECs remained unclear. In this report, we explored the apoptosis and underlying mechanism of BMECs induced by yeast and hypha phases using a pathogen/host cell co-culture model. Our results revealed that both the yeast and hypha phases of could induce BMEC apoptosis; however, the yeast phase induced more cell apoptosis than the hypha phase, as assessed via electronic microscopy and flow cytometry assays. This finding was further corroborated via the measurement of the mitochondrial membrane potential (MMP) and the TUNEL test. Infection by both the yeast and hypha phases of greatly induced the expression of proteins associated with cell death pathways and important components of toll-like receptor (TLR) signaling, including TLR2 and TLR4 receptors, as determined via a Western blotting assay. BMECs mainly underwent apoptosis after infection by the yeast phase through a mitochondrial pathway. Meanwhile, BMEC apoptosis induced by the hypha phase was regulated by a death ligand/receptor pathway. In addition, -induced BMEC apoptosis was regulated by both the TLR2/ERK and JNK/ERK signaling pathways. These data suggest that the yeast phase and hypha phase of induce BMEC apoptosis through distinct cell signaling pathways. This study represents a unique perspective on the molecular processes underlying BMEC apoptosis in response to infection.

摘要

感染某菌属是全球范围内奶牛乳房炎的一个重要病因。我们之前发现,该菌是中国宁夏银川地区奶牛霉菌性乳房炎的主要病原体。然而,这种病原体的感染是否能诱导乳腺上皮细胞(BMECs)凋亡仍不清楚。在本报告中,我们使用病原体/宿主细胞共培养模型,探讨了该菌酵母相和菌丝相诱导BMECs凋亡的情况及潜在机制。我们的结果显示,该菌的酵母相和菌丝相均可诱导BMECs凋亡;然而,通过电子显微镜和流式细胞术检测评估发现,酵母相比菌丝相诱导更多的细胞凋亡。通过测量线粒体膜电位(MMP)和TUNEL检测进一步证实了这一发现。通过蛋白质印迹分析确定,该菌酵母相和菌丝相的感染均极大地诱导了与细胞死亡途径相关的蛋白质以及Toll样受体(TLR)信号传导的重要成分(包括TLR2和TLR4受体)的表达。BMECs在被该菌酵母相感染后主要通过线粒体途径发生凋亡。同时,该菌菌丝相诱导的BMECs凋亡受死亡配体/受体途径调控。此外,该菌诱导的BMECs凋亡受TLR2/ERK和JNK/ERK信号通路调控。这些数据表明,该菌的酵母相和菌丝相通过不同的细胞信号通路诱导BMECs凋亡。本研究为响应该菌感染时BMECs凋亡的分子过程提供了独特的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3043/10603689/272d05154c1d/animals-13-03222-g001.jpg

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