Endocytosis Pathways of Endothelial Cell Derived Exosomes

Banizs, Anna B.; Huang, Tao; Nakamoto, Robert K.; Shi, Weibin; He, Jiang

doi:10.1021/acs.molpharmaceut.8b00765

Cited by 40 publications

(26 citation statements)

References 24 publications

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“…The three classical endocytic pathways are clathrin‐mediated, caveolin‐mediated endocytosis and macropinocytosis . Recent work has indicated that all three of these pathways can mediate occludin internalization in intestinal epithelial TJ, depending on the type of stimulus.…”

Section: Discussionmentioning

confidence: 99%

Occludin endocytosis is involved in the disruption of the intestinal epithelial barrier in a mouse model of alcoholic steatohepatitis

Wang

Chi

et al. 2019

J of Digest Diseases

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Objective: We aimed to investigate the involvement of the endocytosis of occludin, a key component of tight junction (TJ), in the ethanol-induced disassembly of TJ in a model of alcoholic steatohepatitis. Methods: Wild-type mice were fed an ethanol-containing or isocaloric liquid diet for 8 weeks and then assessed for liver injury (histopathology and measurement of serum enzymes), gut permeability (in vivo lactulose/mannitol and ex vivo dye leakage assays), intestinal epithelium ultrastructure (transmission electron microscopy), and intestinal occludin localization (immunofluorescence microscopy). The human intestinal epithelial cell line Caco-2 was also analyzed in vitro for the effects of ethanol on the barrier function (transepithelial electrical resistance), occludin localization (immunofluorescence microscopy and Western blotting), and endocytosis pathways (double-labeling immunofluorescence microscopy with selective pathway inhibitors). Results: The ethanol-fed mice developed steatohepatitis and displayed intestinal barrier dysfunction, the disruption of intestinal TJ, and enhanced intestinal endocytosis of occluding compared with the control mice. In the Caco-2 monolayers, ethanol treatment decreased transepithelial electrical resistance, disrupted TJ formation, and enhanced occludin endocytosis in a dose-and time-dependent manner. These deleterious events were reversed by pretreating the Caco-2 cells with a selective pharmacological inhibitor of macropinocytosis, but not with the inhibitors of clathrin or caveolin-mediated endocytic pathways. Conclusion: Chronic ethanol exposure may increase intestinal permeability by inducing the micropinocytosis of occludin, resulting in the disruption of intestinal TJ.

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Section: Discussionmentioning

confidence: 99%

Occludin endocytosis is involved in the disruption of the intestinal epithelial barrier in a mouse model of alcoholic steatohepatitis

Wang

Chi

et al. 2019

J of Digest Diseases

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“…Disruption of the actin cytoskeleton using Cytochalasin D or Lantrunculin A inhibited sEV uptake by Human Umbilical Vein Cells (HUVECs), confirming that an intact cytoskeleton facilitates sEV internalization [ 93 ]. Chlorpromazine, which blocks clathrin-mediated endocytosis, inhibited sEV uptake by ovarian cancer cells [ 94 ] and endothelial cells [ 95 ], and heparin dose-dependently inhibited sEV uptake by glioblastoma (GBM) cells [ 96 ] and bone marrow stromal cells [ 97 ]. These findings reinforce the notion that targeting the uptake of cancer sEVs is a promising strategy in the development of new cancer therapeutics, and future efforts should focus on small molecules capable of inhibiting cancer sEV uptake and suppressing tumor progression.…”

Section: Evs As Potential Therapeutic Targets In Cancermentioning

confidence: 99%

Extracellular Vesicles in the Development of Cancer Therapeutics

Sun

Burrola

et al. 2020

IJMS

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Extracellular vesicles (EVs) are small lipid bilayer-delimited nanoparticles released from all types of cells examined thus far. Several groups of EVs, including exosomes, microvesicles, and apoptotic bodies, have been identified according to their size and biogenesis. With extensive investigations on EVs over the last decade, it is now recognized that EVs play a pleiotropic role in various physiological processes as well as pathological conditions through mediating intercellular communication. Most notably, EVs have been shown to be involved in cancer initiation and progression and EV signaling in cancer are viewed as potential therapeutic targets. Furthermore, as membrane nanoparticles, EVs are natural products with some of them, such as tumor exosomes, possessing tumor homing propensity, thus leading to strategies utilizing EVs as drug carriers to effectively deliver cancer therapeutics. In this review, we summarize recent reports on exploring EVs signaling as potential therapeutic targets in cancer as well as on developing EVs as therapeutic delivery carriers for cancer therapy. Findings from preclinical studies are primarily discussed, with early phase clinical trials reviewed. We hope to provide readers updated information on the development of EVs as cancer therapeutic targets or therapeutic carriers.

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“…Exosomes are nanosized vesicles (40–160 nm in diameter), whereas ectosomes are larger and more diverse (50 nm–1 μm in diameter) ( Trams et al., 1981 ). Exosomes are derived from the endocytic pathway and the Golgi apparatus ( Banizs et al., 2018 ; Nagano et al., 2019 ). Ectosomes, on the other hand, are formed by direct host cell liberation of the plasma membrane via outward budding and pinching ( Heijnen et al., 1999 ).…”

Section: Ev Biogenesis and Uptakementioning

confidence: 99%

The Dichotomous Role of Extracellular Vesicles in the Central Nervous System

et al. 2020

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Summary Extracellular vesicles (EVs) are important mediators of intercellular communication. Interest in the role of central nervous system (CNS)-derived EVs has been increasing; however, some skepticism of their importance has persisted because many aspects of their biology remain elusive. This ambiguity is largely due to technical barriers that hamper our ability to achieve a comprehensive understanding of their molecular components and mechanisms responsible for their transmission and uptake. However, accumulating evidence supports the notion that EVs play important roles in basic physiological processes within the CNS during neurodevelopment and synaptic plasticity. Interestingly, EVs also act to spread toxic polypeptides in neurodegenerative diseases. Developing a more profound understanding of the role that EVs play in the CNS could lead to the identification of biomarkers and potential vehicles for drug delivery. Here we highlight our current understanding of CNS EVs and summarize our current understanding of their complex role in the CNS.

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Endocytosis Pathways of Endothelial Cell Derived Exosomes

Cited by 40 publications

References 24 publications

Occludin endocytosis is involved in the disruption of the intestinal epithelial barrier in a mouse model of alcoholic steatohepatitis

Occludin endocytosis is involved in the disruption of the intestinal epithelial barrier in a mouse model of alcoholic steatohepatitis

Extracellular Vesicles in the Development of Cancer Therapeutics

The Dichotomous Role of Extracellular Vesicles in the Central Nervous System

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