{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T21:34:43Z","timestamp":1784064883854,"version":"3.55.0"},"reference-count":39,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T00:00:00Z","timestamp":1696982400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014764","name":"China International Medical Foundation","doi-asserted-by":"publisher","award":["Z\u20102018\u201035\u20102002"],"award-info":[{"award-number":["Z\u20102018\u201035\u20102002"]}],"id":[{"id":"10.13039\/501100014764","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81602846"],"award-info":[{"award-number":["81602846"]}],"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":["82272253"],"award-info":[{"award-number":["82272253"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2021MH145"],"award-info":[{"award-number":["ZR2021MH145"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010040","name":"Taishan Scholar Project of Shandong Province","doi-asserted-by":"publisher","award":["tsqn201812159"],"award-info":[{"award-number":["tsqn201812159"]}],"id":[{"id":"10.13039\/501100010040","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Moyamoya disease (MMD) is a rare disorder of the cerebrovascular system. It is a steno\u2010occlusive disease that involves angiogenesis and blood\u2013brain barrier (BBB) disruption. Bradykinin (BK), its metabolite des\u2010Arg9\u2010BK, and receptor (B1R) affect angiogenesis and BBB integrity. In this study, we aimed to investigate the changes in BK, B1R and des\u2010Arg9\u2010BK levels in the serum and brain tissues of patients with MMD and explore the underlying mechanism of these markers in MMD. We obtained the serum samples and superficial temporal artery (STA) tissue of patients with MMD from the Department of Neurosurgery of the Jining First People's Hospital. First, we measured BK, des\u2010Arg9\u2010BK and B1R levels in the serum of patients by means of ELISA. Next, we performed immunofluorescence to determine B1R expression in STA tissues. Finally, we determined the underlying mechanism through Western blot, angiogenesis assay, immunofluorescence, transendothelial electrical resistance and transcytosis assays. Our results demonstrated a significant increase in the BK, des\u2010Arg9\u2010BK and B1R levels in the serum of patients with MMD compared to healthy controls. Furthermore, an increase in the B1R expression level was observed in the STA tissues of patients with MMD. BK and des\u2010Arg9\u2010BK could promote the migratory and proliferative abilities of bEnd.3 cells and inhibited the formation of bEnd.3 cell tubes. In vitro BBB model showed that BK and des\u2010Arg9\u2010BK could reduce claudin\u20105, ZO\u20101 and occluding expression and BBB disruption. To the best of our knowledge, our results show an increase in BK and B1R levels in the serum and STA tissues of patients with MMD. BK and Des\u2010Arg9\u2010BK could inhibit angiogenesis, promote migratory and proliferative capacities of cells, and disrupt BBB integrity. Therefore, regulating BK, des\u2010Arg9\u2010BK and B1R levels in the serum and the brain could be potential strategies for treating patients with MMD.<\/jats:p>","DOI":"10.1111\/jcmm.17989","type":"journal-article","created":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T05:20:12Z","timestamp":1697088012000},"page":"4069-4079","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Bradykinin\u2010bradykinin receptor (<scp>B1R<\/scp>) signalling is involved in the blood\u2013brain barrier disruption in moyamoya disease"],"prefix":"10.1111","volume":"27","author":[{"given":"Haidong","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pharmacy The Affiliated Lianyungang Hospital of Xuzhou Medical University\/The First People's Hospital of Lianyungang\/First Affiliated Hospital of Kangda College of Nanjing Medical University  Lianyungang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxue","family":"Sun","sequence":"additional","affiliation":[{"name":"Translational Pharmaceutical Laboratory, Jining First People's Hospital Shandong First Medical University  Jining China"},{"name":"Institute of Translational Pharmacy Jining Medical Research Academy  Jining China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengfeng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of neurosurgery, Tengzhou Central People's Hospital Jining Medical University  Tengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Translational Pharmaceutical Laboratory, Jining First People's Hospital Shandong First Medical University  Jining China"},{"name":"Institute of Translational Pharmacy Jining Medical Research Academy  Jining China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"Translational Pharmaceutical Laboratory, Jining First People's Hospital Shandong First Medical University  Jining China"},{"name":"Institute of Translational Pharmacy Jining Medical Research Academy  Jining China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nannan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Translational Pharmaceutical Laboratory, Jining First People's Hospital Shandong First Medical University  Jining China"},{"name":"Institute of Translational Pharmacy Jining Medical Research Academy  Jining China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6769-0638","authenticated-orcid":false,"given":"Lei","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Jining First People's Hospital Shandong First Medical University  Jining China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,10,11]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0804622"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10143-018-0994-5"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.2176\/nmc.32.883"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.06.038"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1042\/ns20170139"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.2174\/156720206778018730"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2022.899470"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2013.10.016"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/hypertensionaha.107.097394"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0803624"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.57.1.2"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161206777698710"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00390.2014"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2001.281.1.H275"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.873727"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.10142"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00701-019-03811-w"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.23213"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2022.10.037"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-8467(97)00082-6"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0102382"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11081455"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23203"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3791\/51312"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-009-9146-4"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-014-1519-x"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2016.02.010"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2017.08.042"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1161\/strokeaha.109.547752"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbin.11232"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/5847478"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1690453"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12957-019-1570-3"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ai.2017.05.007"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1254\/jjp.87.318"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2005.01218.x"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.26100"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2019.7380"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00701-020-04480-w"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.17989","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T14:31:42Z","timestamp":1705588302000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.17989"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,11]]},"references-count":39,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2023,12]]}},"alternative-id":["10.1111\/jcmm.17989"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.17989","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,11]]},"assertion":[{"value":"2023-06-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}