The senescent secretome drives PLVAP expression in cultured human hepatic endothelial cells to promote monocyte transmigration.
The senescent secretome drives PLVAP expression in cultured human hepatic endothelial cells to promote monocyte transmigration.
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DOI：
10.1016/j.isci.2023.107966
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发表时间：
2023-10-20
期刊：
影响因子：
5.8
通讯作者：
Shetty, Shishir
中科院分区：
文献类型：
--
作者：
Wilkinson, Alex L.;Hulme, Samuel;Kennedy, James I.;Mann, Emily R.;Horn, Paul;Shepherd, Emma L.;Yin, Kelvin;Zaki, Marco Y. W.;Hardisty, Gareth;Lu, Wei-Yu;Rantakari, Pia;Adams, David H.;Salmi, Marko;Hoare, Matthew;Patten, Daniel A.;Shetty, Shishir
肝窦内皮细胞（LSEC）在慢性肝病（CLD）中经历了显著的表型变化，但驱动这一过程的因素以及对它们作为血管屏障和免疫细胞募集的看门人功能的影响知之甚少。质膜囊泡相关蛋白（PLVAP）已被表征为CLD中LSEC的标志物;值得注意的是，我们发现PLVAP上调与组织衰老的标志物强烈相关。此外，人LSEC暴露于衰老相关分泌表型（SASP）导致PLVAP显著上调。基于流动的分析表明，SASP驱动的白细胞募集的特点是单核细胞的旁细胞迁移，而大多数淋巴细胞的跨细胞迁移。敲除研究证实，PLVAP通过调节磷酸-VE-钙粘蛋白表达和内皮间隙形成，选择性地支持通过PLVAP对LSEC渗透性的影响介导的单核细胞迁移。因此，PLVAP可能代表一种内皮靶点，其选择性地塑造肝病中衰老介导的免疫微环境。PLVAP在人类肝脏疾病中的表达与组织衰老标志物相关当体外暴露于SASP时人类肝脏内皮上调PLVAP PLVAP通过调节磷酸化VE钙粘蛋白水平介导内皮屏障功能PLVAP支持SASP处理的内皮中单核细胞的旁细胞迁移微环境;分子生物学;细胞生物学;组学;转录组学
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. PLVAP expression in human liver disease correlates with markers of tissue senescence Human liver endothelium upregulates PLVAP when exposed to the SASP in vitro PLVAP mediates endothelial barrier function by regulating phospho-VE cadherin levels PLVAP supports paracellular transmigration of monocytes in SASP-treated endothelium Microenvironment; Molecular biology; Cell biology; Omics; Transcriptomics
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影响因子：
16.6
作者：
Ferreira-Gonzalez S;Lu WY;Raven A;Dwyer B;Man TY;O'Duibhir E;Lewis PJS;Campana L;Kendall TJ;Bird TG;Tarrats N;Acosta JC;Boulter L;Forbes SJ
通讯作者：
Forbes SJ
DOI：
10.1146/annurev-cancerbio-030617-050352
发表时间：
2018-01-01
期刊：
ANNUAL REVIEW OF CANCER BIOLOGY, VOL 2
影响因子：
--
作者：
Hoare, Matthew;Narita, Masashi
通讯作者：
Narita, Masashi
影响因子：
64.8
作者：
Kang, Tae-Won;Yevsa, Tetyana;Zender, Lars
通讯作者：
Zender, Lars
影响因子：
25.7
作者：
Asrani, Sumeet K.;Devarbhavi, Harshad;Kamath, Patrick S.
通讯作者：
Kamath, Patrick S.
影响因子：
25.7
作者：
Aravinthan, Aloysious;Scarpini, Cinzia;Alexander, Graeme
通讯作者：
Alexander, Graeme