Treponema pallidum membrane protein Tp47 promotes angiogenesis through ROS ‐induced autophagy

作者：Wei Li, Lin Xie, Qiu‐Ling Li, Qiu‐Yan Xu, Li‐Rong Lin, Li‐Li Liu, Tian‐Ci Yang · 发表于：Journal of the European Academy of Dermatology and Venereology · 年份：2022 · DOI：10.1111/jdv.18728 · 被引用次数：15 · 研究领域：Syphilis Diagnosis and Treatment、Autophagy in Disease and Therapy、Aquaculture disease management and microbiota

BACKGROUND: Pathological angiogenesis is an important manifestation of syphilis, but the underlying mechanism of Treponema pallidum subspecies pallidum (T. pallidum)-induced angiogenesis is poorly understood. OBJECTIVES: The objective of this study is to investigate the role and related mechanism of the T. pallidum membrane protein Tp47 in angiogenesis. METHODS: The proangiogenic activity of recombinant T. pallidum membrane protein Tp47 in human umbilical vein endothelial cells (HUVECs) was assessed by tube formation assay, three-dimensional angiogenesis analysis and experiments with a zebrafish embryo model. The effects of mitochondrial ROS and NADPH oxidase on intracellular ROS induced by Tp47 were further investigated. Furthermore, the levels of autophagy-related proteins and autophagic flux were measured. Finally, the role of ROS-induced autophagy in angiogenesis was studied. RESULTS: Tp47 promoted tubule formation and the formation of angiogenic sprouts in vitro. In addition, a significant increase in the number of subintestinal vessel branch points in zebrafish injected with Tp47 was observed using a zebrafish embryo model. Tp47 also significantly increased intracellular ROS levels in a dose-dependent manner. Tp47-induced tube formation and angiogenic sprout formation were effectively prevented by the ROS inhibitor NAC. In addition, Tp47 enhanced the production of mitochondrial ROS and expression of the NADPH oxidase-related proteins Nox2 and Nox4. The production of mit...