Vermette David, Hu Pamela, Canarie Michael F, Funaro Melissa, Glover Janis, Pierce Richard W
Department of Pediatrics, Yale University, 333 Cedar Street, PO Box 208064, New Haven, CT, 06520, USA.
Cushing/Whitney Medical Library, Yale University, 333 Cedar Street, PO Box 208064, New Haven, CT, 06520, USA.
Intensive Care Med Exp. 2018 Sep 26;6(1):37. doi: 10.1186/s40635-018-0203-4.
Epithelial and endothelial barrier integrity, essential for homeostasis, is maintained by cellular boarder structures known as tight junctions (TJs). In critical illness, TJs may become disrupted, resulting in barrier dysfunction manifesting as capillary leak, pulmonary edema, gut bacterial translocation, and multiple organ failure. We aim to provide a clinically focused overview of TJ structure and function and systematically review and analyze all studies assessing markers of endothelial and epithelial TJ breakdown correlated with clinical outcomes in critically ill humans.
We systematically searched MEDLINE, EMBASE, and PubMed. Additional articles were identified by targeted searches. We included studies that looked at the relationship between biomarkers of endothelial or epithelial TJ structure or function and critical illness. Results were qualitatively analyzed due to sample size and heterogeneity.
A total of 5297 abstracts met search criteria, of which 150 articles met requirements for full text review. Of these, 30 studies met inclusion criteria. Fifteen of the 30 reports investigated proteins of endothelial tight junctions and 15 investigated epithelial TJ markers, exclusively in the gastrointestinal epithelium. No studies investigated TJ-derived proteins in primary cardiac or pulmonary pathology.
TJ integrity is essential for homeostasis. We identified multiple studies that indicate TJs are disrupted by critical illness. These studies highlight the significance of barrier disruption across many critical disease states and correlate TJ-associated markers to clinically relevant outcomes. Further study on the role of multiple tissue-specific claudins, particularly in the setting of respiratory or cardiac failure, may lead to diagnostic and therapeutic advances.
This systematic review is registered in the PROSPERO database: CRD42017074546 .
上皮和内皮屏障的完整性是内环境稳态所必需的，它由称为紧密连接（TJs）的细胞边界结构维持。在危重病中，紧密连接可能会被破坏，导致屏障功能障碍，表现为毛细血管渗漏、肺水肿、肠道细菌移位和多器官功能衰竭。我们旨在提供一份以临床为重点的紧密连接结构和功能概述，并系统地回顾和分析所有评估内皮和上皮紧密连接破坏标志物与危重病患者临床结局相关性的研究。
我们系统地检索了MEDLINE、EMBASE和PubMed。通过定向检索确定了其他文章。我们纳入了研究内皮或上皮紧密连接结构或功能生物标志物与危重病之间关系的研究。由于样本量和异质性，对结果进行了定性分析。
共有5297篇摘要符合检索标准，其中150篇文章符合全文审查要求。其中，30项研究符合纳入标准。30份报告中有15份专门研究了胃肠道上皮中内皮紧密连接的蛋白质，15份研究了上皮紧密连接标志物。没有研究在原发性心脏或肺部疾病中研究紧密连接衍生的蛋白质。
紧密连接的完整性对内环境稳态至关重要。我们发现多项研究表明紧密连接在危重病中被破坏。这些研究强调了在许多危重病状态下屏障破坏的重要性，并将紧密连接相关标志物与临床相关结局相关联。对多种组织特异性闭合蛋白的作用进行进一步研究，特别是在呼吸或心力衰竭的情况下，可能会带来诊断和治疗方面的进展。
本系统评价已在PROSPERO数据库中注册：CRD42017074546 。
