The Epithelial Cell Leak Pathway

Monaco, Ashley; Ovryn, Ben; Axis, Josephine; Amsler, Kurt

doi:10.3390/ijms22147677

Cited by 50 publications

(59 citation statements)

References 201 publications

(353 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These proteins include occludin, members of the claudin family of proteins, and the junctional adhesion molecule (JAM) family of proteins ( 1 , 5 , 12 – 14 ). Occludin plays a role in the formation and disassembly of the TJ and is involved in the regulation of the “leak pathway” or paracellular flux of large molecules ( 1 , 15 – 17 ), whereas claudins have a greater role in controlling the “pore pathway” or paracellular flux of ions and small molecules, and JAMs are important for TJ assembly and facilitating leukocyte adhesion and migration ( 1 , 6 , 11 , 18 – 20 ). The TJ proteins are also directly linked to cytoskeletal actomyosin fibers via cytoplasmic TJ proteins, including the zonula occludens (ZO) family (ZO-1, ZO-2, and ZO-3) ( 1 , 6 , 21 – 23 ).…”

Section: Introductionmentioning

confidence: 99%

IL-1β and the Intestinal Epithelial Tight Junction Barrier

2021

View full text Add to dashboard Cite

The intestinal epithelial tight junction (TJ) barrier controls the paracellular permeation of contents from the intestinal lumen into the intestinal tissue and systemic circulation. A defective intestinal TJ barrier has been implicated as an important pathogenic factor in inflammatory diseases of the gut including Crohn’s disease, ulcerative colitis, necrotizing enterocolitis, and celiac disease. Previous studies have shown that pro-inflammatory cytokines, which are produced during intestinal inflammation, including interleukin-1β (IL-1β), tumor necrosis factor-α, and interferon-γ, have important intestinal TJ barrier-modulating actions. Recent studies have shown that the IL-1β-induced increase in intestinal TJ permeability is an important contributing factor of intestinal inflammation. The IL-1β-induced increase in intestinal TJ permeability is mediated by regulatory signaling pathways and activation of nuclear transcription factor nuclear factor-κB, myosin light chain kinase gene activation, and post-transcriptional occludin gene modulation by microRNA and contributes to the intestinal inflammatory process. In this review, the regulatory role of IL-1β on intestinal TJ barrier, the intracellular mechanisms that mediate the IL-1β modulation of intestinal TJ permeability, and the potential therapeutic targeting of the TJ barrier are discussed.

show abstract

Section: Introductionmentioning

confidence: 99%

IL-1β and the Intestinal Epithelial Tight Junction Barrier

2021

View full text Add to dashboard Cite

show abstract

“…In the above studies, intestinal tight junction proteins were the most commonly used indicators for assessing intestinal damage. When stimulated by factors such as inflammation and oxidative stress, the protein function is damaged and the density of the intestinal barrier is reduced, leading to the “leakage” of inflammatory substances and LPS molecules into the blood circulation, resulting in the occurrence of chronic systemic inflammation ( Monaco et al., 2021 ). Occludin and claudin are transmembrane proteins and ZO is a peripheral membrane scaffold protein, all of which are indispensable components of intestinal tight junctions ( Vancamelbeke and Vermeire, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Gut Microbiota: The Potential Key Target of TCM’s Therapeutic Effect of Treating Different Diseases Using the Same Method—UC and T2DM as Examples

Zhang

Liu

Yang

et al. 2022

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Traditional Chinese herbal medicine often exerts the therapeutic effect of “treating different diseases with the same method” in clinical practice; in other words, it is a kind of herbal medicine that can often treat two or even multiple diseases; however, the biological mechanism underlying its multi-path and multi-target pharmacological effects remains unclear. Growing evidence has demonstrated that gut microbiota dysbiosis plays a vital role in the occurrence and development of several diseases, and that the root cause of herbal medicine plays a therapeutic role in different diseases, a phenomenon potentially related to the improvement of the gut microbiota. We used local intestinal diseases, such as ulcerative colitis, and systemic diseases, such as type 2 diabetes, as examples; comprehensively searched databases, such as PubMed, Web of Science, and China National Knowledge Infrastructure; and summarized the related studies. The results indicate that multiple individual Chinese herbal medicines, such as Rhizoma coptidis (Huang Lian), Curcuma longa L (Jiang Huang), and Radix Scutellariae (Huang Qin), and Chinese medicinal compounds, such as Gegen Qinlian Decoction, Banxia Xiexin Decoction, and Shenling Baizhu Powder, potentially treat these two diseases by enriching the diversity of the gut microbiota, increasing beneficial bacteria and butyrate-producing bacteria, reducing pathogenic bacteria, improving the intestinal mucosal barrier, and inhibiting intestinal and systemic inflammation. In conclusion, this study found that a variety of traditional Chinese herbal medicines can simultaneously treat ulcerative colitis and type 2 diabetes, and the gut microbiota may be a significant target for herbal medicine as it exerts its therapeutic effect of “treating different diseases with the same method”.

show abstract

“…The movement of large solutes across epithelial cell layers by movement through the tight junctions joining adjacent epithelial cells is mediated by the Leak Pathway (for reviews, see Monaco et al, 2021; Otani & Furuse, 2020; Shen et al, 2011). This pathway exhibits a relatively small capacity and is unaffected by the solute charge.…”

Section: Introductionmentioning

confidence: 99%

Simple graphical approach to investigate differences in transepithelial paracellular leak pathway permeability

Monaco

Axis

Amsler

2022

Physiological Reports

Self Cite

View full text Add to dashboard Cite

Although many studies have reported differences in epithelial paracellular Leak Pathway permeability following genetic manipulations and treatment with various agents, the basis for these differences remains mostly unclear. Two primary mechanisms which could underlie differences in Leak Pathway permeability are differences in the density of Leak Pathway openings and differences in the opening size. Using a computational approach, we demonstrate that these two possibilities can be readily distinguished graphically by comparing the apparent paracellular permeabilities of a size panel of solutes measured across different cell layers. Using this approach, we demonstrated that depletion of ZO‐1 protein in MDCK Type II renal epithelial cells decreased Leak Pathway opening size and increased opening density. Depletion of ZO‐2 protein either had no effect or minimally decreased opening size and did not markedly change opening density. Comparison of MDCK Type II cells with MDCK Type I cells revealed that Type I cells exhibited a substantially smaller Leak Pathway permeability than did Type II cells. This lower permeability was due to a decrease in opening density with little or no change in opening size. These results demonstrate the utility of this approach to provide insights into the basis for observed differences in epithelial Leak Pathway permeability. This approach has wide applications including analysis of the molecular basis for Leak Pathway permeability, the effects of specific manipulations on Leak Pathway permeability properties, and the effects of permeation enhancers on Leak Pathway permeability properties.

show abstract

The Epithelial Cell Leak Pathway

Cited by 50 publications

References 201 publications

IL-1β and the Intestinal Epithelial Tight Junction Barrier

IL-1β and the Intestinal Epithelial Tight Junction Barrier

Gut Microbiota: The Potential Key Target of TCM’s Therapeutic Effect of Treating Different Diseases Using the Same Method—UC and T2DM as Examples

Simple graphical approach to investigate differences in transepithelial paracellular leak pathway permeability

Contact Info

Product

Resources

About