{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T14:46:14Z","timestamp":1791816374267,"version":"4.3.4"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,11,25]],"date-time":"2022-11-25T00:00:00Z","timestamp":1669334400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2022,11,25]],"date-time":"2022-11-25T00:00:00Z","timestamp":1669334400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81471967"],"award-info":[{"award-number":["81471967"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81772260"],"award-info":[{"award-number":["81772260"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81973104"],"award-info":[{"award-number":["81973104"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acad Dermatol Venereol"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Pathological angiogenesis is an important manifestation of syphilis, but the underlying mechanism of\n                      <jats:italic>Treponema pallidum<\/jats:italic>\n                      subspecies\n                      <jats:italic>pallidum<\/jats:italic>\n                      (\n                      <jats:italic>T.\u00a0pallidum<\/jats:italic>\n                      )\u2010induced angiogenesis is poorly understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      The objective of this study is to investigate the role and related mechanism of the\n                      <jats:italic>T.\u00a0pallidum<\/jats:italic>\n                      membrane protein Tp47 in angiogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The proangiogenic activity of recombinant\n                      <jats:italic>T.\u00a0pallidum<\/jats:italic>\n                      membrane protein Tp47 in human umbilical vein endothelial cells (HUVECs) was assessed by tube formation assay, three\u2010dimensional 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\u2010related proteins and autophagic flux were measured. Finally, the role of ROS\u2010induced autophagy in angiogenesis was studied.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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\u2010dependent manner. Tp47\u2010induced 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\u2010related 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\u2010related proteins P62 and Beclin 1 and the LC3\u2010II\/LC3\u2010I 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Tp47\u2010induced 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jdv.18728","type":"journal-article","created":{"date-parts":[[2022,11,14]],"date-time":"2022-11-14T03:26:55Z","timestamp":1668396415000},"page":"558-572","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["<i>Treponema pallidum<\/i>\n                    membrane protein Tp47 promotes angiogenesis through\n                    <scp>ROS<\/scp>\n                    \u2010induced autophagy"],"prefix":"10.1111","volume":"37","author":[{"given":"Wei","family":"Li","sequence":"first","affiliation":[{"name":"Center of Clinical Laboratory, Zhongshan Hospital of Xiamen University, School of Medicine Xiamen University  Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Xie","sequence":"additional","affiliation":[{"name":"Center of Clinical Laboratory, Zhongshan Hospital of Xiamen University, School of Medicine Xiamen University  Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiu\u2010Ling","family":"Li","sequence":"additional","affiliation":[{"name":"Center of Clinical Laboratory, Zhongshan Hospital of Xiamen University, School of Medicine Xiamen University  Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiu\u2010Yan","family":"Xu","sequence":"additional","affiliation":[{"name":"Center of Clinical Laboratory, Zhongshan Hospital of Xiamen University, School of Medicine Xiamen University  Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4503-9382","authenticated-orcid":false,"given":"Li\u2010Rong","family":"Lin","sequence":"additional","affiliation":[{"name":"Center of Clinical Laboratory, Zhongshan Hospital of Xiamen University, School of Medicine Xiamen University  Xiamen China"},{"name":"Institute of Infectious Disease, School of Medicine Xiamen University  Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4968-4266","authenticated-orcid":false,"given":"Li\u2010Li","family":"Liu","sequence":"additional","affiliation":[{"name":"Center of Clinical Laboratory, Zhongshan Hospital of Xiamen University, School of Medicine Xiamen University  Xiamen China"},{"name":"Xiamen Clinical Laboratory Quality Control Center  Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4303-6252","authenticated-orcid":false,"given":"Tian\u2010Ci","family":"Yang","sequence":"additional","affiliation":[{"name":"Center of Clinical Laboratory, Zhongshan Hospital of Xiamen University, School of Medicine Xiamen University  Xiamen China"},{"name":"Institute of Infectious Disease, School of Medicine Xiamen University  Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11,25]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.73"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-020-11018-8"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1067\/mjd.2003.504"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep18785"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2019.04.035"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63491-8"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijmm.2017.03.001"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13967"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2019.05.003"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-019-0287-8"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-018-1060-5"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2010.07.007"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2016.12.003"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciu087"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.15725"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-018-9647-0"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2018.11.019"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/polym12061398"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.27806"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10050718"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.06.006"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00026.2013"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9081849"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00346.2016"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2021.102081"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2017.01.007"},{"key":"e_1_2_10_28_1","first-page":"1","article-title":"Immunomodulation by endothelial cells \u2010 partnering up with the immune system?","volume":"14","author":"Amersfoort J","year":"2022","journal-title":"Nat Rev Immunol"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222112035"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-09-512749"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-018-9613-x"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/v8070198"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tube.2020.101943"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2018.09.004"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-021-00435-0"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9061342"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2011.06.033"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2017.11.028"},{"issue":"2","key":"e_1_2_10_39_1","first-page":"262","article-title":"NADPH oxidases in the differentiation of endothelial cells","volume":"116","author":"Hahner F","year":"2020","journal-title":"Cardiovasc Res"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2021.1984656"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2018.7649"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2020.101207"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2019.1644076"}],"container-title":["Journal of the European Academy of Dermatology and Venereology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jdv.18728","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jdv.18728","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jdv.18728","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T13:58:49Z","timestamp":1791813529000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jdv.18728"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,25]]},"references-count":42,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,3]]}},"alternative-id":["10.1111\/jdv.18728"],"URL":"https:\/\/doi.org\/10.1111\/jdv.18728","archive":["Portico"],"relation":{},"ISSN":["0926-9959","1468-3083"],"issn-type":[{"value":"0926-9959","type":"print"},{"value":"1468-3083","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,25]]},"assertion":[{"value":"2022-07-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}