{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T18:09:02Z","timestamp":1793210942006,"version":"4.5.0"},"reference-count":46,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["International Immunopharmacology"],"published-print":{"date-parts":[[2025,2]]},"DOI":"10.1016\/j.intimp.2024.113957","type":"journal-article","created":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T13:01:17Z","timestamp":1736427677000},"page":"113957","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":20,"special_numbering":"C","title":["Heparan sulfate acts in synergy with tight junction through STAT3 signaling to maintain the endothelial barrier and prevent lung injury development"],"prefix":"10.1016","volume":"147","author":[{"given":"Dong","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boyang","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyi","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangyu","family":"Ning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaozhi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"10358","key":"10.1016\/j.intimp.2024.113957_b0005","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1016\/S0140-6736(22)01485-4","article-title":"Acute respiratory distress syndrome: causes, pathophysiology, and phenotypes","volume":"400","author":"Bos","year":"2022","journal-title":"Lancet"},{"issue":"1","key":"10.1016\/j.intimp.2024.113957_b0010","doi-asserted-by":"crossref","DOI":"10.1183\/13993003.02978-2020","article-title":"Mesenchymal stromal cell extracellular vesicles rescue mitochondrial dysfunction and improve barrier integrity in clinically relevant models of ARDS","volume":"58","author":"Dutra Silva","year":"2021","journal-title":"Eur. Respir. J."},{"issue":"6","key":"10.1016\/j.intimp.2024.113957_b0015","doi-asserted-by":"crossref","first-page":"L1085","DOI":"10.1152\/ajplung.00046.2021","article-title":"Inhibition of the lipoxin A4 and resolvin D1 receptor impairs host response to acute lung injury caused by pneumococcal pneumonia in mice","volume":"320","author":"Siegel","year":"2021","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"issue":"1","key":"10.1016\/j.intimp.2024.113957_b0020","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s12933-024-02133-1","article-title":"Heparanase inhibition as a systemic approach to protect theendothelial glycocalyx and prevent microvascular complications in diabetes","volume":"23","author":"Gamez","year":"2024","journal-title":"Cardiovasc. Diabetol."},{"issue":"5","key":"10.1016\/j.intimp.2024.113957_b0025","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s00018-022-04260-y","article-title":"Rapid shear stress-dependent ENaC membrane insertion is mediated by the endothelial glycocalyx and the mineralocorticoid receptor","volume":"79","author":"Cosgun","year":"2022","journal-title":"Cell Mol. Life Sci."},{"issue":"1","key":"10.1016\/j.intimp.2024.113957_b0030","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/s13054-024-04875-6","article-title":"Vascular leak in sepsis: physiological basis and potential therapeutic advances","volume":"28","author":"McMullan","year":"2024","journal-title":"Crit. Care"},{"issue":"2","key":"10.1016\/j.intimp.2024.113957_b0035","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.kint.2023.03.039","article-title":"Hemolysis is associated with altered heparan sulfate of the endothelial glycocalyx and with local complement activation in thrombotic microangiopathies","volume":"104","author":"Laboux","year":"2023","journal-title":"Kidney Int."},{"issue":"2","key":"10.1016\/j.intimp.2024.113957_b0040","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1111\/jth.14371","article-title":"Derangement of the endothelial glycocalyx in sepsis","volume":"17","author":"Iba","year":"2019","journal-title":"J. Thromb. Haemost."},{"key":"10.1016\/j.intimp.2024.113957_b0045","article-title":"Heparanase as active player in endothelial glycocalyx remodeling","volume":"13","author":"Masola","year":"2021","journal-title":"Matrix Biol. plus"},{"issue":"8","key":"10.1016\/j.intimp.2024.113957_b0050","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1038\/nm.2843","article-title":"The pulmonary endothelial glycocalyx regulates neutrophil adhesion and lung injury during experimental sepsis","volume":"18","author":"Schmidt","year":"2012","journal-title":"Nat. Med."},{"issue":"7","key":"10.1016\/j.intimp.2024.113957_b0055","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1182\/blood-2013-07-514984","article-title":"Nonanticoagulant heparin prevents histone-mediated cytotoxicity in vitro and improves survival in sepsis","volume":"123","author":"Wildhagen","year":"2014","journal-title":"Blood"},{"issue":"1","key":"10.1016\/j.intimp.2024.113957_b0060","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s40635-018-0203-4","article-title":"Tight junction structure, function, and assessment in the critically ill: a systematic review","volume":"6","author":"Vermette","year":"2018","journal-title":"Intensive Care Med. Exp."},{"issue":"1","key":"10.1016\/j.intimp.2024.113957_b0065","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s12931-024-02688-3","article-title":"HDAC6-selective inhibitor CAY10603 ameliorates cigarette smoke-induced small airway remodeling by regulating epithelial barrier dysfunction and reversing","volume":"25","author":"Zhang","year":"2024","journal-title":"Respir. Res."},{"issue":"6","key":"10.1016\/j.intimp.2024.113957_b0070","doi-asserted-by":"crossref","first-page":"L584","DOI":"10.1152\/ajplung.00211.2014","article-title":"Changes in endothelial connexin 43 expression inversely correlate with microvessel permeability and VE-cadherin expression in endotoxin-challenged lungs","volume":"309","author":"Kandasamy","year":"2015","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"issue":"10","key":"10.1016\/j.intimp.2024.113957_b0075","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0186116","article-title":"Regeneration of glycocalyx by heparan sulfate and sphingosine 1-phosphate restores inter-endothelial communication","volume":"12","author":"Mensah","year":"2017","journal-title":"PLoS One"},{"issue":"8","key":"10.1016\/j.intimp.2024.113957_b0080","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.1097\/MIB.0000000000000421","article-title":"Syndecan-1 acts in synergy with tight junction through Stat3 signaling to maintain intestinal mucosal barrier and prevent bacterial translocation","volume":"21","author":"Wang","year":"2015","journal-title":"Inflamm. Bowel. Dis."},{"issue":"1","key":"10.1016\/j.intimp.2024.113957_b0085","doi-asserted-by":"crossref","DOI":"10.1111\/bpa.13006","article-title":"Glycocalyx is critical for blood-brain barrier integrity by suppressing caveolin1-dependent endothelial transcytosis following ischemic stroke","volume":"32","author":"Zhu","year":"2022","journal-title":"Brain Pathol."},{"issue":"10","key":"10.1016\/j.intimp.2024.113957_b0090","doi-asserted-by":"crossref","first-page":"e1034","DOI":"10.1002\/iid3.1034","article-title":"Heat stress combined with lipopolysaccharide induces pulmonary microvascular endothelial cell glycocalyx inflammatory damage in vitro","volume":"11","author":"Chen","year":"2023","journal-title":"Immun. Inflamm. Dis."},{"key":"10.1016\/j.intimp.2024.113957_b0095","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.intimp.2018.10.001","article-title":"Berberine alleviates endothelial glycocalyx degradation and promotes glycocalyx restoration in LPS-induced ARDS","volume":"65","author":"Huang","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.intimp.2024.113957_b0100","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2020.111026","article-title":"Alveolar epithelial glycocalyx shedding aggravates the epithelial barrier and disrupts epithelial tight junctions in acute respiratory distress syndrome","volume":"133","author":"Li","year":"2021","journal-title":"Biomed. Pharmacother."},{"issue":"7662","key":"10.1016\/j.intimp.2024.113957_b0105","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nature22978","article-title":"The extracellular matrix protein agrin promotes heart regeneration in mice","volume":"547","author":"Bassat","year":"2017","journal-title":"Nature"},{"issue":"2","key":"10.1016\/j.intimp.2024.113957_b0110","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/s41401-019-0255-3","article-title":"ZYZ-803, a novel hydrogen sulfide-nitric oxide conjugated donor, promotes angiogenesis via cross-talk between STAT3 and CaMKII","volume":"41","author":"Xiong","year":"2020","journal-title":"Acta Pharmacol. Sin."},{"issue":"4","key":"10.1016\/j.intimp.2024.113957_b0115","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1369\/0022155417692536","article-title":"Heparanase mediates intestinal inflammation and injury in a mouse model of sepsis","volume":"65","author":"Chen","year":"2017","journal-title":"J. Histochem. Cytochem."},{"key":"10.1016\/j.intimp.2024.113957_b0120","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejps.2020.105400","article-title":"Therapeutic effects of mangiferin on sepsis-associated acute lung and kidney injuries via the downregulation of vascular permeability and protection of inflammatory and oxidative damages","volume":"152","author":"Zhang","year":"2020","journal-title":"Eur. J. Pharm. Sci."},{"issue":"9","key":"10.1016\/j.intimp.2024.113957_b0125","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1016\/j.ajpath.2021.05.015","article-title":"Recombinant antithrombin attenuates acute respiratory distress syndrome in experimental endotoxemia","volume":"191","author":"Okamoto","year":"2021","journal-title":"Am. J. Pathol."},{"issue":"5","key":"10.1016\/j.intimp.2024.113957_b0130","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1111\/all.16030","article-title":"A humanized mouse model to study asthmatic airway remodeling and Muc-5ac secretion via the human IL-33","volume":"79","author":"Zhang","year":"2024","journal-title":"Allergy"},{"issue":"5","key":"10.1016\/j.intimp.2024.113957_b0135","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1002\/jcp.25575","article-title":"Endothelial STAT3 activation increases vascular leakage through downregulating tight junction proteins: implications for diabetic retinopathy","volume":"232","author":"Yun","year":"2017","journal-title":"J. Cell Physiol."},{"issue":"11","key":"10.1016\/j.intimp.2024.113957_b0140","doi-asserted-by":"crossref","first-page":"400","DOI":"10.3390\/jcm7110400","article-title":"Shared features of endothelial dysfunction between sepsis and its preceding risk factors (aging and chronic disease)","volume":"7","author":"Bermejo-Martin","year":"2018","journal-title":"J. Clin. Med."},{"issue":"1","key":"10.1016\/j.intimp.2024.113957_b0145","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1136\/thoraxjnl-2018-211535","article-title":"Fas activation alters tight junction proteins in acute lung injury","volume":"74","author":"Herrero","year":"2019","journal-title":"Thorax"},{"issue":"5","key":"10.1016\/j.intimp.2024.113957_b0150","doi-asserted-by":"crossref","first-page":"H1672","DOI":"10.1152\/ajpheart.00832.2003","article-title":"Inflammation- and ischemia-induced shedding of venular glycocalyx","volume":"286","author":"Mulivor","year":"2004","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"issue":"4","key":"10.1016\/j.intimp.2024.113957_b0155","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1152\/japplphysiol.00436.2005","article-title":"Short-term hyperglycemia increases endothelial glycocalyx permeability and acutely decreases lineal density of capillaries with flowing red blood cells","volume":"99","author":"Zuurbier","year":"2005","journal-title":"J. Appl. Physiol."},{"issue":"7874","key":"10.1016\/j.intimp.2024.113957_b0160","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41586-021-03818-3","article-title":"APRIL limits atherosclerosis by binding to heparan sulfate proteoglycans","volume":"597","author":"Tsiantoulas","year":"2021","journal-title":"Nature"},{"issue":"6","key":"10.1016\/j.intimp.2024.113957_b0165","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1097\/SHK.0000000000002130","article-title":"Pulmonary vascular endothelial glycocalyx degradation contributes to acute lung injury in experiencing heat stroke","volume":"59","author":"Cao","year":"2023","journal-title":"Shock"},{"issue":"2","key":"10.1016\/j.intimp.2024.113957_b0170","first-page":"913","article-title":"Both UFH and NAH alleviate shedding of endothelial glycocalyx and coagulopathy in LPS-induced sepsis","volume":"19","author":"Huang","year":"2020","journal-title":"Exp. Ther. Med."},{"issue":"6","key":"10.1016\/j.intimp.2024.113957_b0175","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S1537-1891(02)00200-8","article-title":"Tight junctions of the blood-brain barrier: development, composition and regulation","volume":"38","author":"Wolburg","year":"2002","journal-title":"Vascul. Pharmacol."},{"issue":"45","key":"10.1016\/j.intimp.2024.113957_b0180","doi-asserted-by":"crossref","first-page":"29745","DOI":"10.1074\/jbc.273.45.29745","article-title":"The tight junction protein ZO-1 establishes a link between the transmembrane protein occludin and the actin cytoskeleton","volume":"273","author":"Fanning","year":"1998","journal-title":"J. Biol. Chem."},{"issue":"35","key":"10.1016\/j.intimp.2024.113957_b0185","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2304168120","article-title":"Gap junction-transported cAMP from the niche controls stem cell progeny differentiation","volume":"120","author":"Tu","year":"2023","journal-title":"Proc. Natl. Acad. Sci. U S a."},{"issue":"25","key":"10.1016\/j.intimp.2024.113957_b0190","doi-asserted-by":"crossref","DOI":"10.1002\/adhm.202300696","article-title":"Supramolecular assemblies of glycopeptides enhance gap junction maturation of human induced pluripotent stem cell-derived cardiomyocytes via inducing spheroids formation to optimize cardiac repair","volume":"12","author":"Li","year":"2023","journal-title":"Adv. Healthc. Mater."},{"issue":"7","key":"10.1016\/j.intimp.2024.113957_b0195","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.7150\/thno.29400","article-title":"Mitochondrial transfer from bone marrow mesenchymal stem cells to motor neurons in spinal cord injury rats via gap junction","volume":"9","author":"Li","year":"2019","journal-title":"Theranostics"},{"issue":"8","key":"10.1016\/j.intimp.2024.113957_b0200","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1172\/JCI26605","article-title":"Connexin 43 mediates spread of Ca2+-dependent proinflammatory responses in lung capillaries","volume":"116","author":"Parthasarathi","year":"2006","journal-title":"J. Clin. Invest."},{"issue":"1","key":"10.1016\/j.intimp.2024.113957_b0205","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1002\/jcp.20647","article-title":"Possible involvement of gap junctions in the barrier function of tight junctions of brain and lung endothelial cells","volume":"208","author":"Nagasawa","year":"2006","journal-title":"J. Cell Physiol."},{"issue":"2","key":"10.1016\/j.intimp.2024.113957_b0210","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1007\/s00441-014-1969-7","article-title":"The heparan sulfate proteoglycan agrin contributes to barrier properties of mouse brain endothelial cells by stabilizing adherens junctions","volume":"358","author":"Steiner","year":"2014","journal-title":"Cell Tissue Res."},{"issue":"19","key":"10.1016\/j.intimp.2024.113957_b0215","doi-asserted-by":"crossref","first-page":"20392","DOI":"10.1074\/jbc.M308710200","article-title":"Role of Src-induced dynamin-2 phosphorylation in caveolae-mediated endocytosis in endothelial cells","volume":"279","author":"Shajahan","year":"2004","journal-title":"J. Biol. Chem."},{"issue":"41","key":"10.1016\/j.intimp.2024.113957_b0220","doi-asserted-by":"crossref","first-page":"25968","DOI":"10.1074\/jbc.272.41.25968","article-title":"Gp60 activation mediates albumin transcytosis in endothelial cells by tyrosine kinase-dependent pathway","volume":"272","author":"Tiruppathi","year":"1997","journal-title":"J. Biol. Chem."},{"issue":"8","key":"10.1016\/j.intimp.2024.113957_b0225","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1161\/01.RES.0000245187.08026.47","article-title":"Novel mechanism of endothelial nitric oxide synthase activation mediated by caveolae internalization in endothelial cells","volume":"99","author":"Maniatis","year":"2006","journal-title":"Circ. Res."},{"issue":"1","key":"10.1016\/j.intimp.2024.113957_b0230","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1186\/s12967-018-1721-2","article-title":"Pro-atherosclerotic disturbed flow disrupts caveolin-1 expression, localization, and function via glycocalyx degradation","volume":"16","author":"Harding","year":"2018","journal-title":"J. Transl. Med."}],"container-title":["International Immunopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1567576924024792?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1567576924024792?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T04:25:07Z","timestamp":1740111907000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1567576924024792"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2]]},"references-count":46,"alternative-id":["S1567576924024792"],"URL":"https:\/\/doi.org\/10.1016\/j.intimp.2024.113957","relation":{},"ISSN":["1567-5769"],"issn-type":[{"value":"1567-5769","type":"print"}],"subject":[],"published":{"date-parts":[[2025,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Heparan sulfate acts in synergy with tight junction through STAT3 signaling to maintain the endothelial barrier and prevent lung injury development","name":"articletitle","label":"Article Title"},{"value":"International Immunopharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.intimp.2024.113957","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"113957"}}