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The senescent secretome drives PLVAP expression in cultured human hepatic endothelial cells to promote monocyte transmigration.

التفاصيل البيبلوغرافية
العنوان: The senescent secretome drives PLVAP expression in cultured human hepatic endothelial cells to promote monocyte transmigration.
المؤلفون: Wilkinson AL; Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK., Hulme S; Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK., Kennedy JI; Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK., Mann ER; Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK., Horn P; Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK., Shepherd EL; College of Health and Life Sciences, Aston University, Birmingham B4 7ET, UK., Yin K; University of Cambridge, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge CB2 0RE, UK., Zaki MYW; Department of Biochemistry, Faculty of Pharmacy, Minia University, Minia, Egypt., Hardisty G; Centre for Inflammation Research, University of Edinburgh, Edinburgh EH8 9YL, UK., Lu WY; Centre for Inflammation Research, University of Edinburgh, Edinburgh EH8 9YL, UK., Rantakari P; Institute of Biomedicine, University of Turku, Turku, Finland.; MediCity Research Laboratory, University of Turku, Turku, Finland., Adams DH; Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK., Salmi M; Institute of Biomedicine, University of Turku, Turku, Finland.; MediCity Research Laboratory, University of Turku, Turku, Finland., Hoare M; University of Cambridge, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge CB2 0RE, UK.; University of Cambridge, Department of Medicine, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK., Patten DA; Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK.; National Institute for Health Research, Birmingham Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK., Shetty S; Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK.; National Institute for Health Research, Birmingham Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
المصدر: IScience [iScience] 2023 Sep 19; Vol. 26 (10), pp. 107966. Date of Electronic Publication: 2023 Sep 19 (Print Publication: 2023).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 101724038 Publication Model: eCollection Cited Medium: Internet ISSN: 2589-0042 (Electronic) Linking ISSN: 25890042 NLM ISO Abbreviation: iScience Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [Cambridge, MA] : Cell Press, [2018]-
مستخلص: Liver sinusoidal endothelial cells (LSEC) undergo significant phenotypic change in chronic liver disease (CLD), and yet the factors that drive this process and the impact on their function as a vascular barrier and gatekeeper for immune cell recruitment are poorly understood. Plasmalemma-vesicle-associated protein (PLVAP) has been characterized as a marker of LSEC in CLD; notably we found that PLVAP upregulation strongly correlated with markers of tissue senescence. Furthermore, exposure of human LSEC to the senescence-associated secretory phenotype (SASP) led to a significant upregulation of PLVAP. Flow-based assays demonstrated that SASP-driven leukocyte recruitment was characterized by paracellular transmigration of monocytes while the majority of lymphocytes migrated transcellularly. Knockdown studies confirmed that PLVAP selectively supported monocyte transmigration mediated through PLVAP's impact on LSEC permeability by regulating phospho-VE-cadherin expression and endothelial gap formation. PLVAP may therefore represent an endothelial target that selectively shapes the senescence-mediated immune microenvironment in liver disease.
Competing Interests: S.S. is a consultant for Faron Pharmaceuticals.
(© 2023 The Author(s).)
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معلومات مُعتمدة: 26813 United Kingdom CRUK_ Cancer Research UK; MR/R010013/1 United Kingdom MRC_ Medical Research Council; 29959 United Kingdom CRUK_ Cancer Research UK; United Kingdom WT_ Wellcome Trust; MR/X00970X/1 United Kingdom MRC_ Medical Research Council
فهرسة مساهمة: Keywords: Cell biology; Microenvironment; Molecular biology; Omics; Transcriptomics
تواريخ الأحداث: Date Created: 20231009 Latest Revision: 20240320
رمز التحديث: 20240320
مُعرف محوري في PubMed: PMC10558774
DOI: 10.1016/j.isci.2023.107966
PMID: 37810232
قاعدة البيانات: MEDLINE
الوصف
تدمد:2589-0042
DOI:10.1016/j.isci.2023.107966