{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T10:02:39Z","timestamp":1790244159157,"version":"4.1.0"},"reference-count":49,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2019,8,1]],"date-time":"2019-08-01T00:00:00Z","timestamp":1564617600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,8,1]],"date-time":"2019-08-01T00:00:00Z","timestamp":1564617600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","ibroneuroscience.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Neuroscience"],"published-print":{"date-parts":[[2019,8]]},"DOI":"10.1016\/j.neuroscience.2019.06.008","type":"journal-article","created":{"date-parts":[[2019,6,18]],"date-time":"2019-06-18T02:38:48Z","timestamp":1560825528000},"page":"123-134","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":50,"special_numbering":"C","title":["LRG1 Promotes Apoptosis and Autophagy through the TGF\u03b2-smad1\/5 Signaling Pathway to Exacerbate Ischemia\/Reperfusion Injury"],"prefix":"10.1016","volume":"413","author":[{"given":"Jing","family":"Jin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxue","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haining","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongping","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guozhong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.neuroscience.2019.06.008_bb0005","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1189\/jlb.1107751","article-title":"LRG-accelerated differentiation defines unique G-CSFR signaling pathways downstream of PU.1 and C\/EBPepsilon that modulate neutrophil activation","volume":"83","author":"Ai","year":"2008","journal-title":"J Leukoc Biol"},{"issue":"Suppl 1","key":"10.1016\/j.neuroscience.2019.06.008_bb0010","doi-asserted-by":"crossref","first-page":"30","DOI":"10.3109\/14767058.2012.663176","article-title":"Autophagy in hypoxia\u2013ischemia induced brain injury","volume":"25","author":"Balduini","year":"2012","journal-title":"J Matern Fetal Neonatal Med"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0015","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1002\/ana.21174","article-title":"Prediction of hemorrhagic transformation after recanalization therapy using T2*-permeability magnetic resonance imaging","volume":"62","author":"Bang","year":"2007","journal-title":"Ann Neurol"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0020","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s10495-009-0412-0","article-title":"Cytochrome c-induced lymphocyte death from the outside in: inhibition by serum leucine-rich alpha-2-glycoprotein-1","volume":"15","author":"Codina","year":"2010","journal-title":"Apoptosis"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0025","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1007\/s10495-006-8159-3","article-title":"Serum leucine-rich alpha-2-glycoprotein-1 binds cytochrome c and inhibits antibody detection of this apoptotic marker in enzyme-linked immunosorbent assay","volume":"11","author":"Cummings","year":"2006","journal-title":"Apoptosis"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0030","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/nrn.2016.51","article-title":"Autophagy in acute brain injury","volume":"17","author":"Galluzzi","year":"2016","journal-title":"Nat Rev Neurosci"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0035","doi-asserted-by":"crossref","first-page":"e1696","DOI":"10.1038\/cddis.2015.36","article-title":"Autophagy is a regulator of TGF-beta1-induced fibrogenesis in primary human atrial myofibroblasts","volume":"6","author":"Ghavami","year":"2015","journal-title":"Cell Death Dis"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0040","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.brainres.2006.03.086","article-title":"Neuroprotection against ischemic brain injury by SP600125 via suppressing the extrinsic and intrinsic pathways of apoptosis","volume":"1092","author":"Guan","year":"2006","journal-title":"Brain Res"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0045","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.bbrc.2017.05.099","article-title":"Autophagy-related gene microarray and bioinformatics analysis for ischemic stroke detection","volume":"489","author":"Guo","year":"2017","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0050","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1186\/s12967-016-0929-2","article-title":"LRG1 downregulation in allergic airway disorders and its expression in peripheral blood and tissue cells","volume":"14","author":"Hao","year":"2016","journal-title":"J Transl Med"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0055","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1515\/bchm2.1977.358.1.639","article-title":"Isolation and characterization of an unknown, leucine-rich 3.1-S-alpha2-glycoprotein from human serum (author's transl)","volume":"358","author":"Haupt","year":"1977","journal-title":"Hoppe Seylers Z Physiol Chem"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0060","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1681\/ASN.2018060599","article-title":"LRG1 promotes diabetic kidney disease progression by enhancing TGF-beta-induced angiogenesis","volume":"30","author":"Hong","year":"2019","journal-title":"J Am Soc Nephrol"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0065","doi-asserted-by":"crossref","first-page":"8844","DOI":"10.1158\/0008-5472.CAN-08-4401","article-title":"Autophagy is activated by TGF-beta and potentiates TGF-beta-mediated growth inhibition in human hepatocellular carcinoma cells","volume":"69","author":"Kiyono","year":"2009","journal-title":"Cancer Res"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0070","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1016\/j.cell.2007.10.035","article-title":"Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice","volume":"131","author":"Komatsu","year":"2007","journal-title":"Cell"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0075","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1093\/cvr\/cvv273","article-title":"Myeloid cell-derived LRG attenuates adverse cardiac remodelling after myocardial infarction","volume":"109","author":"Kumagai","year":"2016","journal-title":"Cardiovasc Res"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0080","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.jns.2011.08.048","article-title":"Blood-brain barrier permeability derangements in posterior circulation ischemic stroke: frequency and relation to hemorrhagic transformation","volume":"313","author":"Lee","year":"2012","journal-title":"J Neurol Sci"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0085","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1007\/s00701-006-0787-4","article-title":"Analysis of potential diagnostic biomarkers in cerebrospinal fluid of idiopathic normal pressure hydrocephalus by proteomics","volume":"148","author":"Li","year":"2006","journal-title":"Acta Neurochir"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0090","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.neulet.2006.11.039","article-title":"Expression of TGF-betas and TGF-beta type II receptor in cerebrospinal fluid of patients with idiopathic normal pressure hydrocephalus","volume":"413","author":"Li","year":"2007","journal-title":"Neurosci Lett"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0095","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.tcm.2015.04.010","article-title":"Burden of stroke in women","volume":"26","author":"Lundberg","year":"2016","journal-title":"Trends Cardiovasc Med"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0100","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/S1474-4422(11)70066-7","article-title":"Stroke and the immune system: from pathophysiology to new therapeutic strategies","volume":"10","author":"Macrez","year":"2011","journal-title":"Lancet Neurol"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0105","doi-asserted-by":"crossref","first-page":"5535","DOI":"10.3892\/mmr.2016.5925","article-title":"LRG1 promotes angiogenesis through upregulating the TGFbeta1 pathway in ischemic rat brain","volume":"14","author":"Meng","year":"2016","journal-title":"Mol Med Rep"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0110","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0074453","article-title":"Leucine-rich alpha2-glycoprotein is a novel biomarker of neurodegenerative disease in human cerebrospinal fluid and causes neurodegeneration in mouse cerebral cortex","volume":"8","author":"Miyajima","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0115","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.neuron.2010.07.002","article-title":"The science of stroke: mechanisms in search of treatments","volume":"67","author":"Moskowitz","year":"2010","journal-title":"Neuron"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0120","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1007\/s00701-011-0963-z","article-title":"Leucine-rich alpha-2-glycoprotein is a marker for idiopathic normal pressure hydrocephalus","volume":"153","author":"Nakajima","year":"2011","journal-title":"Acta Neurochir"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0125","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1189\/jlb.72.3.478","article-title":"Molecular characterization and expression analysis of leucine-rich alpha2-glycoprotein, a novel marker of granulocytic differentiation","volume":"72","author":"O'Donnell","year":"2002","journal-title":"J Leukoc Biol"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0130","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1038\/nm.3097","article-title":"Tsc1 (hamartin) confers neuroprotection against ischemia by inducing autophagy","volume":"19","author":"Papadakis","year":"2013","journal-title":"Nat Med"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0135","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1210\/jc.2014-3855","article-title":"Elevation of a novel angiogenic factor, leucine-rich-alpha2-glycoprotein (LRG1), is associated with arterial stiffness, endothelial dysfunction, and peripheral arterial disease in patients with type 2 diabetes","volume":"100","author":"Pek","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0140","doi-asserted-by":"crossref","DOI":"10.1002\/dmrr.3029","article-title":"Association of circulating proinflammatory marker, leucine-rich-alpha2-glycoprotein (LRG1), following metabolic\/bariatric surgery","volume":"34","author":"Pek","year":"2018","journal-title":"Diabetes Metab Res Rev"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0145","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1016\/j.molonc.2016.07.004","article-title":"LRG1 mRNA expression in breast cancer associates with PIK3CA genotype and with aromatase inhibitor therapy outcome","volume":"10","author":"Ramirez-Ardila","year":"2016","journal-title":"Mol Oncol"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0150","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1136\/ard.2009.118919","article-title":"iTRAQ-based proteomic identification of leucine-rich alpha-2 glycoprotein as a novel inflammatory biomarker in autoimmune diseases","volume":"69","author":"Serada","year":"2010","journal-title":"Ann Rheum Dis"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0155","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1093\/ecco-jcc\/jjw132","article-title":"Leucine-rich alpha-2 glycoprotein is a serum biomarker of mucosal healing in ulcerative colitis","volume":"11","author":"Shinzaki","year":"2017","journal-title":"J Crohns Colitis"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0160","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1016\/j.bbrc.2009.03.104","article-title":"Up-regulation of the expression of leucine-rich alpha(2)-glycoprotein in hepatocytes by the mediators of acute-phase response","volume":"382","author":"Shirai","year":"2009","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0165","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.nbd.2010.09.014","article-title":"Autophagy in acute brain injury: feast, famine, or folly?","volume":"43","author":"Smith","year":"2011","journal-title":"Neurobiol Dis"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0170","doi-asserted-by":"crossref","first-page":"645","DOI":"10.4161\/auto.6.5.12046","article-title":"Regulation of autophagy by transforming growth factor-beta (TGF-beta) signaling","volume":"6","author":"Suzuki","year":"2010","journal-title":"Autophagy"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0175","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1073\/pnas.82.7.1906","article-title":"Periodicity of leucine and tandem repetition of a 24-amino acid segment in the primary structure of leucine-rich alpha 2-glycoprotein of human serum","volume":"82","author":"Takahashi","year":"1985","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0180","doi-asserted-by":"crossref","first-page":"11009","DOI":"10.18632\/oncotarget.3557","article-title":"Leucine-rich alpha-2-glycoprotein promotes TGFbeta1-mediated growth suppression in the Lewis lung carcinoma cell lines","volume":"6","author":"Takemoto","year":"2015","journal-title":"Oncotarget"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0185","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.stemcr.2017.06.008","article-title":"Reactive astrocytes promote ALS-like degeneration and intracellular protein aggregation in human motor neurons by disrupting autophagy through TGF-beta1","volume":"9","author":"Tripathi","year":"2017","journal-title":"Stem Cell Reports"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0190","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.bbi.2016.10.004","article-title":"Neuroanatomical correlates of stroke-associated infection and stroke-induced immunodepression","volume":"60","author":"Urra","year":"2017","journal-title":"Brain Behav Immun"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0195","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1186\/s13075-017-1349-2","article-title":"Leucine-rich alpha 2 glycoprotein promotes Th17 differentiation and collagen-induced arthritis in mice through enhancement of TGF-beta-Smad2 signaling in naive helper T cells","volume":"19","author":"Urushima","year":"2017","journal-title":"Arthritis Res Ther"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0200","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1161\/01.STR.32.2.424","article-title":"Reproducibility of measurements of cerebral infarct volume on CT scans","volume":"32","author":"van der Worp","year":"2001","journal-title":"Stroke"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0205","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1038\/nature12345","article-title":"LRG1 promotes angiogenesis by modulating endothelial TGF-beta signalling","volume":"499","author":"Wang","year":"2013","journal-title":"Nature"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0210","doi-asserted-by":"crossref","first-page":"e2715","DOI":"10.1038\/cddis.2017.129","article-title":"TNF-alpha-induced LRG1 promotes angiogenesis and mesenchymal stem cell migration in the subchondral bone during osteoarthritis","volume":"8","author":"Wang","year":"2017","journal-title":"Cell Death Dis"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0215","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1161\/CIRCHEARTFAILURE.110.952200","article-title":"Proteomic analysis of coronary sinus serum reveals leucine-rich alpha2-glycoprotein as a novel biomarker of ventricular dysfunction and heart failure","volume":"4","author":"Watson","year":"2011","journal-title":"Circ Heart Fail"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0220","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1111\/cas.13329","article-title":"Overexpression of leucine-rich alpha2-glycoprotein-1 is a prognostic marker and enhances tumor migration in gastric cancer","volume":"108","author":"Yamamoto","year":"2017","journal-title":"Cancer Sci"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0225","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.eurpsy.2014.03.004","article-title":"Plasma-based proteomics reveals lipid metabolic and immunoregulatory dysregulation in post-stroke depression","volume":"29","author":"Zhan","year":"2014","journal-title":"Eur Psychiatry"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0230","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1007\/s12032-015-0598-7","article-title":"LRG1 suppresses the migration and invasion of hepatocellular carcinoma cells","volume":"32","author":"Zhang","year":"2015","journal-title":"Med Oncol"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0235","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s13046-016-0306-2","article-title":"LRG1 modulates epithelial\u2013mesenchymal transition and angiogenesis in colorectal cancer via HIF-1alpha activation","volume":"35","author":"Zhang","year":"2016","journal-title":"J Exp Clin Cancer Res"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0240","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1046\/j.1471-4159.2003.01756.x","article-title":"Bcl-2 overexpression protects against neuron loss within the ischemic margin following experimental stroke and inhibits cytochrome c translocation and caspase-3 activity","volume":"85","author":"Zhao","year":"2003","journal-title":"J Neurochem"},{"key":"10.1016\/j.neuroscience.2019.06.008_bb0245","article-title":"LRG1 promotes proliferation and inhibits apoptosis in colorectal cancer cells via RUNX1 activation","volume":"12","author":"Zhou","year":"2017","journal-title":"PLoS One"}],"container-title":["Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0306452219304142?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0306452219304142?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,5]],"date-time":"2025-10-05T15:50:23Z","timestamp":1759679423000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0306452219304142"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8]]},"references-count":49,"alternative-id":["S0306452219304142"],"URL":"https:\/\/doi.org\/10.1016\/j.neuroscience.2019.06.008","relation":{},"ISSN":["0306-4522"],"issn-type":[{"value":"0306-4522","type":"print"}],"subject":[],"published":{"date-parts":[[2019,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"LRG1 Promotes Apoptosis and Autophagy through the TGF\u03b2-smad1\/5 Signaling Pathway to Exacerbate Ischemia\/Reperfusion Injury","name":"articletitle","label":"Article Title"},{"value":"Neuroscience","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.neuroscience.2019.06.008","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 IBRO. Published by Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}