Dysfunction of epithelial permeability barrier induced by HMGB1 in 2.5D cultures of human epithelial cells

Kojima, Takashi; Shindo, Yuma; Konno, Takumi; Kodera, Yuki; Arai, Wataru; Miyakawa, Maki; Ohwada, Kizuku; Tanaka, Hiroki; Tsujiwaki, Mitsuhiro; Sakuma, Yoshiki; Kikuchi, Satoshi; Ohkuni, Tsuyoshi; Takano, Kenichi; Watanabe, Atsushi; Kohno, Takayuki

doi:10.1080/21688370.2021.1972760

Cited by 5 publications

(3 citation statements)

References 106 publications

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“…Our previous study has detected severe damage and necroptosis that occurred in the cecum of TNF-induced SIRS mice 9 . More speci cally, consolidated evidence has also suggested that cecum damage increased circulating HMGB1 levels and elevated in ammatory cytokines released by over-activated microglia and led to a neurological disorder, thereafter 39,40 . In our study, SIRS mice receiving cecectomy surprisingly improved SIRS mice outcomes, including decreasing circulating HMGB1 level, improving BBB permeability, and inhibiting over-activated microglia.…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Ketamine alleviated blood-brain barrier damage and microglia over-activation induced by SIRS via restricting cecum damage and HMGB1 release

Deng

Yang

et al. 2022

Preprint

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Following systemic inflammatory response syndrome (SIRS), the brain is one of the most sensitive organs vulnerable to an external stressor. According to our previous study, ketamine had a protective effect on alleviating SIRS-associated neuronal necroptosis and cecal epithelial cell necroptosis by inhibiting the RIP1-RIP3-MLKL pathway. In this study, we further provided valid evidence that ketamine could safeguard the integrity of the blood-brain barrier (BBB), modulate microglia over-activation, and prevent neural network damage, resulting in relieving cerebral edema and improving system symptoms significantly. Simultaneously, cecum damage was partly reversed by ketamine intervention, which was attributed to a decrease in circulating high mobility group protein 1 (HMGB1). Interestingly, the result showed less cecum injury and relieved BBB disturbance in Rip3-/- mice. Furthermore, circulating HMGB1 content between Rip3-/- mice and mice with ketamine intervention significantly decreased. Moreover, anti-HMGB1 neutralizing antibody identically reversed BBB damage, indicating that cecum-promoted HMGB1 releases extravagated SIRS and BBB leakage. In addition, we clarified that cecectomy reduced serum HMGB1 release level and alleviated BBB damage and microglial activation. Altogether, our work shed light on the new view about the pathogenesis of SIRS, establishing the connection between cecum damage and BBB damage. Besides, we identified ketamine as a candidate to protect the brain from damage like BBB leakage and microglia over-activation, which attributed to the effect on alleviating cecum damage and decreasing circulation HMGB1 release. Our results provided a new theoretical view and therapeutic target for the application of ketamine in SIRS.

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Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Ketamine alleviated blood-brain barrier damage and microglia over-activation induced by SIRS via restricting cecum damage and HMGB1 release

Deng

Yang

et al. 2022

Preprint

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“…The AJs are critical for cell-cell contact at the basolateral surface, and the TJ proteins play an important role in relaying the molecular signal to its intracellular molecular partners from the periphery of the cells. [181,182] (iii) MARVELD3: two isoforms (iii) Both isoforms contain four transmembrane domains and N-and C-terminal cytoplasmic domains (iii) Genetic expression in lung cancer cells [183] (2) Claudins 27 claudin protein family members; claudin-13 not expressed in humans [60] Structural domains of claudins are similar to occludin despite differences in amino acid sequences Claudin-3, claudin-4, and claudin-7 are detected in type II alveolar epithelial cells, and claudin-18.1 is most abundant in type I alveolar epithelial cells [184,185]. Claudin-3 and claudin-4 are also expressed by type I epithelial cells [96] (3) Ig superfamily proteins Junctional adhesion molecules (JAM) and coxsackievirus B adenovirus receptor (CAR) JAM and CAR proteins contain an extracellular domain with two Ig-like domains, a single transmembrane segment, and a cytoplasmic tail with a Post-synaptic density protein 95, Drosophila disc large tumor suppressor, and Zonula occludens (ZO-1) or PDZ domain-binding motif [186][187][188].…”

Section: Airway and Alveolar Epitheliummentioning

confidence: 99%

Tight Junctions, the Epithelial Barrier, and Toll-like Receptor-4 During Lung Injury

et al. 2022

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Lung epithelium is constantly exposed to the environment and is critically important for the orchestration of initial responses to infectious organisms, toxins, and allergic stimuli, and maintenance of normal gaseous exchange and pulmonary function. The integrity of lung epithelium, fluid balance, and transport of molecules is dictated by the tight junctions (TJs). The TJs are formed between adjacent cells. We have focused on the topic of the TJ structure and function in lung epithelial cells. This review includes a summary of the last twenty years of literature reports published on the disrupted TJs and epithelial barrier in various lung conditions and expression and regulation of specific TJ proteins against pathogenic stimuli. We discuss the molecular signaling and crosstalk among signaling pathways that control the TJ structure and function. The Toll-like receptor-4 (TLR4) recognizes the pathogen-and damage-associated molecular patterns released during lung injury and inflammation and coordinates cellular responses. The molecular aspects of TLR4 signaling in the context of TJs or the epithelial barrier are not fully known. We describe the current knowledge and possible networking of the TLR4-signaling with cellular and molecular mechanisms of TJs, lung epithelial barrier function, and resistance to treatment strategies.

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“…TGF-β is associated with increased migration and malignant transformation of endometrial carcinomas through activation of estrogen-related receptor alpha (ERRα); it is also associated with invasion and epithelial-to-mesenchymal transition (EMT) [ 64 ]. TGF-β increases HMGB1 expression and induces changes in LSR localization and downregulation, resulting in reduced epithelial barrier homeostasis [ 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 ]. TGF-β levels are also elevated in high-grade stages of endometriosis [ 73 ].…”

Section: Lsr-related Molecular Mechanisms Leading To Disruption Of En...mentioning

confidence: 99%

Atypical Macropinocytosis Contributes to Malignant Progression: A Review of Recent Evidence in Endometrioid Endometrial Cancer Cells

Kohno

Kojima²

2022

Cancers

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Macropinocytosis is an essential mechanism for the non-specific uptake of extracellular fluids and solutes. In recent years, additional functions have been identified in macropinocytosis, such as the intracellular introduction pathway of drugs, bacterial and viral infection pathways, and nutritional supplement pathway of cancer cells. However, little is known about the changes in cell function after macropinocytosis. Recently, it has been reported that macropinocytosis is essential for endometrial cancer cells to initiate malignant progression in a dormant state. Macropinocytosis is formed by a temporary split of adjacent bicellular junctions of epithelial sheets, rather than from the apical surface or basal membrane, as a result of the transient reduction of tight junction homeostasis. This novel type of macropinocytosis has been suggested to be associated with the malignant pathology of endometriosis and endometrioid endometrial carcinoma. This review outlines the induction of malignant progression of endometrial cancer cells by macropinocytosis based on a new mechanism and the potential preventive mechanism of its malignant progression.

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Dysfunction of epithelial permeability barrier induced by HMGB1 in 2.5D cultures of human epithelial cells

Cited by 5 publications

References 106 publications

WITHDRAWN: Ketamine alleviated blood-brain barrier damage and microglia over-activation induced by SIRS via restricting cecum damage and HMGB1 release

WITHDRAWN: Ketamine alleviated blood-brain barrier damage and microglia over-activation induced by SIRS via restricting cecum damage and HMGB1 release

Tight Junctions, the Epithelial Barrier, and Toll-like Receptor-4 During Lung Injury

Atypical Macropinocytosis Contributes to Malignant Progression: A Review of Recent Evidence in Endometrioid Endometrial Cancer Cells

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