{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T23:29:41Z","timestamp":1776727781819,"version":"3.51.2"},"reference-count":52,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T00:00:00Z","timestamp":1601337600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010877","name":"Science, Technology and Innovation Commission of Shenzhen Municipality","doi-asserted-by":"publisher","award":["JCYJ20170413165705083"],"award-info":[{"award-number":["JCYJ20170413165705083"]}],"id":[{"id":"10.13039\/501100010877","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010877","name":"Science, Technology and Innovation Commission of Shenzhen Municipality","doi-asserted-by":"publisher","award":["SGLH20180625142404672"],"award-info":[{"award-number":["SGLH20180625142404672"]}],"id":[{"id":"10.13039\/501100010877","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010877","name":"Science, Technology and Innovation Commission of Shenzhen Municipality","doi-asserted-by":"publisher","award":["ZDSYS20190902093409851"],"award-info":[{"award-number":["ZDSYS20190902093409851"]}],"id":[{"id":"10.13039\/501100010877","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771243"],"award-info":[{"award-number":["81771243"]}],"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":["81771293"],"award-info":[{"award-number":["81771293"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2021,1]]},"abstract":"Abstract<\/jats:title>Aims<\/jats:title>The canonical Wnt signaling pathway plays an essential role in blood\u2010brain barrier integrity and intracerebral hemorrhage in preclinical stroke models. Here, we sought to explore the association between canonical Wnt signaling and hemorrhagic transformation (HT) following intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients as well as to determine the underlying cellular mechanisms.<\/jats:p><\/jats:sec>Methods<\/jats:title>355 consecutive AIS patients receiving IVT were included. Blood samples were collected on admission, and HT was detected at 24\u00a0hours after IVT. 117 single\u2010nucleotide polymorphisms (SNPs) of 28 Wnt signaling genes and exon sequences of 4 core cerebrovascular Wnt signaling components (GPR124<\/jats:italic>, RECK<\/jats:italic>, FZD4,<\/jats:italic> and CTNNB1<\/jats:italic>) were determined using a customized sequencing chip. The impact of identified genetic variants was further studied in HEK 293T cells using cellular and biochemical assays.<\/jats:p><\/jats:sec>Results<\/jats:title>During the study period, 80 patients experienced HT with 27 parenchymal hematoma (PH). Compared to the non\u2010PH patients, WNT7A<\/jats:italic> SNPs (rs2163910, P<\/jats:italic>\u00a0=\u00a0.001, OR 2.727; rs1124480, P<\/jats:italic>\u00a0=\u00a0.002, OR 2.404) and GPR124<\/jats:italic> SNPs (rs61738775, P<\/jats:italic>\u00a0=\u00a0.012, OR 4.883; rs146016051, P<\/jats:italic>\u00a0<\u00a0.001, OR 7.607; rs75336000, P<\/jats:italic>\u00a0=\u00a0.044, OR 2.503) were selectively enriched in the PH patients. Interestingly, a missense variant of GPR124<\/jats:italic> (rs75336000, c.3587G>A) identified in the PH patients resulted in a single amino acid alteration (p.Cys1196Tyr) in the intracellular domain of GPR124. This variant substantially reduced the activity of WNT7B\u2010induced canonical Wnt signaling by decreasing the ability of GPR124 to recruit cytoplasmic DVL1 to the cellular membrane.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Variants of WNT7A<\/jats:italic> and GPR124<\/jats:italic> are associated with increased risk of PH in patients with AIS after intravenous thrombolysis, likely through regulating the activity of canonical Wnt signaling.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.13457","type":"journal-article","created":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T21:36:05Z","timestamp":1601415365000},"page":"71-81","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Variants of WNT7A<\/i> and GPR124<\/i> are associated with hemorrhagic transformation following intravenous thrombolysis in ischemic stroke"],"prefix":"10.1111","volume":"27","author":[{"given":"Song","family":"Ta","sequence":"first","affiliation":[{"name":"Department of Neurology The First Hospital of Jilin University Changchun China"},{"name":"Shenzhen Key Laboratory of Biomimetic Materials and Cellular Immunomodulation, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianfang","family":"Rong","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Biomimetic Materials and Cellular Immunomodulation, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen\u2010Ni","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Hospital of Jilin University Changchun China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hang","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Hospital of Jilin University Changchun China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Hospital of Jilin University Changchun China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fenge","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Hospital of Jilin University Changchun China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhihuan","family":"Li","sequence":"additional","affiliation":[{"name":"Dongguan Enlife Stem Cell Biotechnology Institute Dongguan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lilong","family":"Lin","sequence":"additional","affiliation":[{"name":"Dongguan Enlife Stem Cell Biotechnology Institute Dongguan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenqing","family":"Zheng","sequence":"additional","affiliation":[{"name":"Shenzhen RealOmics Biotech Co., Ltd. Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingquan","family":"Gu","sequence":"additional","affiliation":[{"name":"Shenzhen RealOmics Biotech Co., Ltd. Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Central Laboratory, Shenzhen Second People's Hospital, Shenzhen University 1st Affiliated Hospital Shenzhen University School of Medicine Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenlan","family":"Liu","sequence":"additional","affiliation":[{"name":"The Central Laboratory, Shenzhen Second People's Hospital, Shenzhen University 1st Affiliated Hospital Shenzhen University School of Medicine Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Hospital of Jilin University Changchun China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0319-9022","authenticated-orcid":false,"given":"Junlei","family":"Chang","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Biomimetic Materials and Cellular Immunomodulation, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,9,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000485"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30500-3"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199512143332401"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0804656"},{"key":"e_1_2_8_6_1","first-page":"19123","article-title":"Advances in stroke pharmacology","author":"Zhou Z","year":"2018","journal-title":"Pharmacol Ther"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X18805926"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2013.203"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000254524.23708.c9"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X18798162"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X19881449"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.30.11.2280"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.10.067"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-018-1815-1"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X20911331"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X18801467"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2015.08.003"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31828406de"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200319212"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20199"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000144051.32131.09"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4309"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2008.08.005"},{"key":"e_1_2_8_24_1","article-title":"A review of the mechanisms of blood\u2010brain barrier permeability by tissue\u2010type plasminogen activator treatment for cerebral ischemia","volume":"102","author":"Suzuki Y","year":"2016","journal-title":"Front Cell Neurosci"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.117.017283"},{"key":"e_1_2_8_26_1","article-title":"Caveolin\u20101 regulates perivascular aquaporin\u20104 expression after cerebral ischemia","volume":"8371","author":"Filchenko I","year":"2020","journal-title":"Front Cell Dev Biol"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X18769515"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1498"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1787"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0907606"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1164594"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.10.042"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1813217115"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0805165106"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1196554"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1017192108"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1019761108"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2014.08.018"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.12.020"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI76431"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.06489"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.07.031"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.015982"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200806024"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1139\/bcb-2018-0384"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-019-1539-9"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-015-9607-2"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aat1178"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)00163-X"},{"key":"e_1_2_8_50_1","article-title":"Circulating tpa contributes to neurovascular coupling by a mechanism involving the endothelial nmda receptors","author":"Anfray A","year":"2019","journal-title":"J Cereb Blood Flow Metab"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20111580"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.09.045"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a034728"}],"container-title":["CNS Neuroscience & Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cns.13457","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cns.13457","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cns.13457","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,2]],"date-time":"2023-09-02T09:01:02Z","timestamp":1693645262000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cns.13457"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,29]]},"references-count":52,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["10.1111\/cns.13457"],"URL":"https:\/\/doi.org\/10.1111\/cns.13457","archive":["Portico"],"relation":{},"ISSN":["1755-5930","1755-5949"],"issn-type":[{"value":"1755-5930","type":"print"},{"value":"1755-5949","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,29]]},"assertion":[{"value":"2020-07-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}