Tight junction structure, function, and assessment in the critically ill: a systematic review

Abstract

BackgroundEpithelial 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.MethodsWe 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.ResultsA 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.ConclusionsTJ 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.Systematic review registrationThis systematic review is registered in the PROSPERO database: CRD42017074546.Electronic supplementary materialThe online version of this article (10.1186/s40635-018-0203-4) contains supplementary material, which is available to authorized users.

Exposure to Zinc Oxide Nanoparticles Disrupts Endothelial Tight and Adherens Junctions and Induces Pulmonary Inflammatory Cell Infiltration

“…Vascular endothelium serves as a first line of defense against injury to blood vessels and the underlying tissues. Endothelium functions as a barrier and dynamically regulates the exchanges of substances between blood stream and the blood vessel wall; dysfunction of endothelial barrier may increase infiltration of blood proteins, toxic agents and immune cells into the vessel wall, resulting in various diseases [7]. The endothelial barrier function is achieved by a transcellular system and coordinated opening and closure of cell-cell junctions [8].…”

Fecal microbiota transplantation reconstructs the gut microbiota of septic mice and protects the intestinal mucosal barrier

“…The main functions of occludin are regulation and sealing of TJs [41,42]. That ZO-1 outperformed other TJ markers may re ect the concomitant organ epithelial injury which occurs in MODS [36]. Therefore, we observed the expression of the above two proteins at 24 and 48 h in the three groups, and the results showed that occludin and ZO-1 in the CLP group were signi cantly lower than those in the Sham group and the FMT group.…”

“…Tight junctions play an important role in maintaining the integrity of the mucosal epithelium [34,35], and it is generally de ned as life-threatening organ failure in the setting of critical illness [36,37]. The barrier function is mediated by changes in the tight junctions and associated proteins and allows out ow of luminal contents and likely damages distant organs, which may contribute to MODS [12].…”

<p>The Cytoplasmic Expression Of CLDN12 Predicts An Unfavorable Prognosis And Promotes Proliferation And Migration Of Osteosarcoma</p>

“…CLDNs are integral components of TJs, and its membrane expression maintain paracellular permeability and are critical for epithelial cell polarity. 19 It is revealed that the change of expression level and localization of CLDNs was an important cause of tumor development. 29,30 For example, a concurrent cytoplasmic subcellular location of CLDN1 expression is associated with malignant canine thyroid tumors and their vascular invasion thyroid tumors.…”

“…Generally, CLDNs are integral membrane proteins localized at tight junctions, which are responsible for establishing and maintaining epithelial cell polarity and it is accepted that the CLDNs are low expressed in the mesenchymal cells. [17][18][19] At present, there are also several literatures on CLDNs in sarcomas. For instance, the expression of CLDN4, −7 and 10 were found expressed in biphasic synovial sarcomas, and CLDN1 expression was also identified in 63% of Ewing's sarcoma family tumors.…”