{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T21:28:48Z","timestamp":1789939728228,"version":"4.0.1"},"reference-count":66,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,5,9]],"date-time":"2022-05-09T00:00:00Z","timestamp":1652054400000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS102745"],"award-info":[{"award-number":["NS102745"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000097","name":"National Center for Research Resources","doi-asserted-by":"publisher","award":["C06RR0306551"],"award-info":[{"award-number":["C06RR0306551"]}],"id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["AG029493"],"award-info":[{"award-number":["AG029493"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Physiological Reports"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Vitronectin (VTN) is a glycoprotein enriched in the blood and activates integrin receptors. VTN blood levels increase only in female mice 24\u00a0h after an ischemic stroke and exacerbate brain injury through IL\u20106\u2010driven inflammation, but the VTN induction mechanism is unknown. Here, a 30\u00a0min middle cerebral artery occlusion (MCAO) in female mice induced VTN protein in the liver (normally the main source) in concert with plasma VTN. Male mice were excluded as VTN is not induced after stroke. MCAO also increased plasma VTN levels after de novo expression of VTN in the liver of VTN<jats:sup>\u2212\/\u2212<\/jats:sup> female mice, using a hepatocyte\u2010specific (<jats:italic>SERPINA1<\/jats:italic>) promoter. MCAO did not affect SERPINA1 or VTN mRNA in the liver, brain, or several peripheral organs, or platelet VTN, compared to sham mice. Thus, hepatocytes are the source of stroke\u2010induced increases in plasma VTN, which is independent of transcription. The cholinergic innervation by the parasympathetic vagus nerve is a potential source of brain\u2010liver signaling after stroke. Right\u2010sided vagotomy at the cervical level led to increased plasma VTN levels, suggesting that VTN release is inhibited by vagal tone. Co\u2010culture of hepatocytes with cholinergic neurons or treatment with acetylcholine, but not noradrenaline (sympathetic transmitter), suppressed VTN expression. Hepatocytes have muscarinic receptors and the M1\/M3 agonist bethanechol decreased VTN mRNA and protein release in vitro via M1 receptors. Finally, systemic bethanechol treatment blocked stroke\u2010induced plasma VTN. Thus, VTN translation and release are inhibited by muscarinic signaling from the vagus nerve and presents a novel target for lessening detrimental VTN expression.<\/jats:p>","DOI":"10.14814\/phy2.15301","type":"journal-article","created":{"date-parts":[[2022,5,9]],"date-time":"2022-05-09T09:49:00Z","timestamp":1652089740000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Liver vitronectin release into the bloodstream increases due to reduced vagal muscarinic signaling after cerebral stroke in female mice"],"prefix":"10.14814","volume":"10","author":[{"given":"Matthew P.","family":"Keasey","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences Quillen College of Medicine East Tennessee State University  Johnson City Tennessee United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiharu","family":"Lovins","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Quillen College of Medicine East Tennessee State University  Johnson City Tennessee United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuihong","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Quillen College of Medicine East Tennessee State University  Johnson City Tennessee United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6117-8836","authenticated-orcid":false,"given":"Theo","family":"Hagg","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Quillen College of Medicine East Tennessee State University  Johnson City Tennessee United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,5,9]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10877\u2010012\u20109424\u20103"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12975\u2010016\u20100450\u20101"},{"key":"e_1_2_8_4_1","first-page":"143","article-title":"The rat dorsal vagal nucleus: Features of cellular and synaptic structure","volume":"45","author":"Akmayev I. G.","year":"1994","journal-title":"Acta Biologica Hungarica"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1160\/TH11\u201003\u20100179"},{"key":"e_1_2_8_6_1","first-page":"43","article-title":"Disorders of the autonomic nervous system after hemispheric cerebrovascular disorders: An update","volume":"8","author":"Al\u2010Qudah Z. A.","year":"2015","journal-title":"Journal of Vascular and Interventional Neurology"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/elps.201700407"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brs.2015.11.008"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010018\u201027306\u20103"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0218133"},{"key":"e_1_2_8_11_1","first-page":"2643","article-title":"Morphology and growth, tumorigenicity, and cytogenetics of human neuroblastoma cells in continuous culture","volume":"33","author":"Biedler J. L.","year":"1973","journal-title":"Cancer Research"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi8017015"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP271539"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X18793324"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2014.00107"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1006\/gyno.1996.0225"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2009.113"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0b013e3181f48a37"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00138.2013"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2015.06.007"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-9065-8_12"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.115.010477"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2012.11"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCINTERVENTIONS.108.795799"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00302.2014"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440\u20101681.1994.tb02545.x"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2007.07.015"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2019.06.041"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2006\u20101419"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2017.05.002"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c120018"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2019.113088"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2018.11.002"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.120.029036"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2012.08.020"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.202580"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/1478\u2010811X\u201011\u201035"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2019.01.012"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1053\/hupa.2001.29675"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/0301\u20100082(83)90016\u20103"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.4199\/C00004ED1V01Y200910ISP001"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.2337\/db09\u20100522"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2009.5"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3302046"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/joa.12448"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M401279200"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.12.8158"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2010.08.009"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.3791\/59803"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0148308"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cb.07.110191.001423"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20100031\u20101276590"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2018.02.056"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.1091910106"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1357\u20102725(99)00005\u20109"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01462292"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021\u20109258(17)32096\u20103"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.155.6.3180"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.21.9402"},{"key":"e_1_2_8_60_1","first-page":"783","article-title":"Quantitation of spreading factor in human biologic fluids","volume":"103","author":"Shaffer M. C.","year":"1984","journal-title":"Journal of Laboratory and Clinical Medicine"},{"key":"e_1_2_8_61_1","first-page":"53193","article-title":"Differentiation of the SH\u2010SY5Y human neuroblastoma cell line","volume":"108","author":"Shipley M. M.","year":"2016","journal-title":"Journal of Visualized Experiments: Jove"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2008.141"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2015.06.004"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0024\u20103205(02)02506\u20107"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.115.010835"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brs.2018.01.034"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2010.01.006"}],"container-title":["Physiological Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.14814\/phy2.15301","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.14814\/phy2.15301","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.14814\/phy2.15301","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,17]],"date-time":"2024-01-17T02:22:53Z","timestamp":1705458173000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.14814\/phy2.15301"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5]]},"references-count":66,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2022,5]]}},"alternative-id":["10.14814\/phy2.15301"],"URL":"https:\/\/doi.org\/10.14814\/phy2.15301","archive":["Portico"],"relation":{},"ISSN":["2051-817X","2051-817X"],"issn-type":[{"value":"2051-817X","type":"print"},{"value":"2051-817X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5]]},"assertion":[{"value":"2022-02-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e15301"}}