Treponema pallidum membrane protein Tp47 promotes angiogenesis through ROS-induced autophagy.
Animals
Humans
Autophagy
Autophagy-Related Proteins
/ pharmacology
Human Umbilical Vein Endothelial Cells
/ metabolism
Membrane Proteins
/ metabolism
NADPH Oxidases
/ metabolism
Neovascularization, Pathologic
Reactive Oxygen Species
/ metabolism
Syphilis
/ microbiology
Treponema pallidum
/ physiology
Zebrafish
Journal
Journal of the European Academy of Dermatology and Venereology : JEADV
ISSN: 1468-3083
Titre abrégé: J Eur Acad Dermatol Venereol
Pays: England
ID NLM: 9216037
Informations de publication
Date de publication:
Mar 2023
Mar 2023
Historique:
received:
12
07
2022
accepted:
06
10
2022
pubmed:
15
11
2022
medline:
16
2
2023
entrez:
14
11
2022
Statut:
ppublish
Résumé
Pathological angiogenesis is an important manifestation of syphilis, but the underlying mechanism of Treponema pallidum subspecies pallidum (T. pallidum)-induced angiogenesis is poorly understood. The objective of this study is to investigate the role and related mechanism of the T. pallidum membrane protein Tp47 in angiogenesis. 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. 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 mitochondrial ROS and intracellular ROS was reduced by the NADPH oxidase inhibitors DPI and apocynin. Furthermore, Tp47 significantly increased expression of the autophagy-related proteins P62 and Beclin 1 and the LC3-II/LC3-I ratio and promoted an increase in autophagic flux, which could be effectively rescued by coincubation with the ROS inhibitor NAC. Further intervention with the autophagy inhibitor BafA1 significantly inhibited tube formation and angiogenic sprout formation. Tp47-induced NADPH oxidase enhanced intracellular ROS production via mitochondrial ROS and promoted angiogenesis through autophagy mediated by ROS. These findings may contribute to our understanding of pathological angiogenesis in syphilis.
Sections du résumé
BACKGROUND
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
OBJECTIVE
The objective of this study is to investigate the role and related mechanism of the T. pallidum membrane protein Tp47 in angiogenesis.
METHODS
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
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 mitochondrial ROS and intracellular ROS was reduced by the NADPH oxidase inhibitors DPI and apocynin. Furthermore, Tp47 significantly increased expression of the autophagy-related proteins P62 and Beclin 1 and the LC3-II/LC3-I ratio and promoted an increase in autophagic flux, which could be effectively rescued by coincubation with the ROS inhibitor NAC. Further intervention with the autophagy inhibitor BafA1 significantly inhibited tube formation and angiogenic sprout formation.
CONCLUSIONS
CONCLUSIONS
Tp47-induced NADPH oxidase enhanced intracellular ROS production via mitochondrial ROS and promoted angiogenesis through autophagy mediated by ROS. These findings may contribute to our understanding of pathological angiogenesis in syphilis.
Substances chimiques
Autophagy-Related Proteins
0
Membrane Proteins
0
NADPH Oxidases
EC 1.6.3.-
Reactive Oxygen Species
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
558-572Subventions
Organisme : Key projects of the Natural Science Foundation of Fujian Province
ID : 2022J02055
Organisme : National Natural Science Foundation of China
ID : 81471967
Organisme : National Natural Science Foundation of China
ID : 81772260
Organisme : National Natural Science Foundation of China
ID : 81973104
Organisme : The Key Projects for Province Science and Technology Program of Fujian Province, China
ID : 2018D0014
Organisme : The Natural Science Foundation of Fujian Province, China
ID : 2021J02055
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022 European Academy of Dermatology and Venereology.
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