Transient cytochalasin-D treatment induces apically administered rAAV2 across tight junctions for transduction of enterocytes

Fu, Ya–Yuan; Sibley, Eric; Tang, Shiue–Cheng

doi:10.1099/vir.0.2008/001446-0

Cited by 8 publications

(3 citation statements)

References 26 publications

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“…4, f-actin relocalizes to a certain extent to the vicinity of the cell membrane, as indicated by the transformation of its striated pattern that spans across multiple cells to a more cobblestone one. The transition from fibers traversing through the cytoplasm to their localization to the cell periphery is the possible consequence of the mechanochemical stress imposed by the particles onto the epithelial membrane [25]. Similar structural alterations of f-actin cytoskeleton, leading to its condensation in pericellular bands, have been previously observed under the effect of substances that disrupt the intestinal epithelial barrier [26].…”

Section: Resultsmentioning

confidence: 84%

PEGylated silicon nanowire coated silica microparticles for drug delivery across intestinal epithelium

et al. 2012

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Composite particles made by growing nanoscopic silicon wires from the surface of monodispersed, microsized silica beads were tested in this study for their ability to affect the integrity and permeability of an epithelial cell layer. Polyethylene glycol (PEG) is known to sterically stabilize particles and prevent protein binding; as such, it is a routine way to impart in vivo longevity to drug carriers. The effect of the silica beads, both with and without silicon nanowires and PEG, on the disruption of the tight junctions in Caco-2 cells was evaluated by means of: (a) analysis of the localization of zonula occludens-1 (ZO-1), claudin-1 and f-actin; (b) measurements of trans-epithelial electrical resistance (TEER); (c) real-time quantitative RT-PCR analysis of the expression of PKC-α and PKC-z, which regulate the fluidity of cell membranes, and RhoA and Rac1, which are mainly involved in mechanotransduction processes; and (d) drug permeability experiments with fluorescein-sodium. The results have shown that Si-nanowire-coated silica microparticles added to Caco-2 cells in culture lead to alterations in tight junction permeability and the localization of ZO-1 and f-actin, as well as to decreased width of ZO-1 and claudin-1 at the tight junction and increased expression of PKC transcripts. Si-nanowire-coated silica microparticles increased the permeability of Caco-2 cell monolayers to fluorescein-sodium in proportion to their amount. Effects indicative of loosening the Caco-2 cell monolayers and increasing their permeability were less pronounced for PEGylated particles, owing to their greater supposed inertness in comparison with the non-functionalized beads and nanowires. The analyzed Si-nanowire-coated silica microparticles have thus been shown to affect membrane barrier integrity in vitro, suggesting the possibility of using nanostructured microparticles to enhance drug permeability through the intestinal epithelium in vivo.

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Section: Resultsmentioning

confidence: 84%

PEGylated silicon nanowire coated silica microparticles for drug delivery across intestinal epithelium

et al. 2012

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“…Moreover, we have previously confirmed that the decline in TEER was not the result of a decrease in cell viability caused by viral infection (Hui et al 2020 ). Meanwhile, it has been reported that CytoD disrupts actin filaments and TJ barriers of intestinal epithelial cells (Fu et al 2008 ), and that TNF-α mediated restructuring of the SCB in vitro involves actin cytoskeleton reorganization (Lydka et al 2012 ). We observed a similar phenomenon in the in vitro mSCB model, CytoD or TNF-α treatment perturbed the SCB in a time- and dose-dependent manner when compared with the control treatment (Fig.…”

Section: Resultsmentioning

confidence: 99%

Rearrangement of Actin Cytoskeleton by Zika Virus Infection Facilitates Blood–Testis Barrier Hyperpermeability

et al. 2021

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In recent years, various serious diseases caused by Zika virus (ZIKV) have made it impossible to be ignored. Confirmed existence of ZIKV in semen and sexually transmission of ZIKV suggested that it can break the blood–testis barrier (BTB), or Sertoli cell barrier (SCB). However, little is known about the underlying mechanism. In this study, interaction between actin, an important component of the SCB, and ZIKV envelope (E) protein domain III (EDIII) was inferred from co-immunoprecipitation (Co-IP) liquid chromatography–tandem mass spectrometry (LC–MS/MS) analysis. Confocal microscopy confirmed the role of actin filaments (F-actin) in ZIKV infection, during which part of the stress fibers, the bundles that constituted by paralleled actin filaments, were disrupted and presented in the cell periphery. Colocalization of E and reorganized actin filaments in the cell periphery of transfected Sertoli cells suggests a participation of ZIKV E protein in ZIKV-induced F-actin rearrangement. Perturbation of F-actin by cytochalasin D (CytoD) or Jasplakinolide (Jas) enhanced the infection of ZIKV. More importantly, the transepithelial electrical resistance (TEER) of an in vitro mouse SCB (mSCB) model declined with the progression of ZIKV infection or overexpression of E protein. Co-IP and confocal microscopy analyses revealed that the interaction between F-actin and tight junction protein ZO-1 was reduced after ZIKV infection or E protein overexpression, highlighting the role of E protein in ZIKV-induced disruption of the BTB. We conclude that the interaction between ZIKV E and F-actin leads to the reorganization of F-actin network, thereby compromising BTB integrity.

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“…To knock out the cytoskeleton, cells were incubated for two hours with cytochalasin D, a fungal mycotoxin which transiently prevents actin polymerization in Caco-2 cells (see Figure 5a–b)[28, 29]. A significant proportion of NEMPs were retained under flow in comparison to the rapid loss of MPs (Figure 5g).…”

Section: Resultsmentioning

confidence: 99%

Hierarchical nanoengineered surfaces for enhanced cytoadhesion and drug delivery

et al. 2011

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Delivering therapeutics to mucosal tissues such as the nasal and gastrointestinal tracts, is highly desirable due to ease of access and dense vasculature. However, the mucus layer effectively captures and removes most therapeutic macromolecules and devices. In previous work, we have shown that nanoengineered microparticles (NEMPs) adhere through the mucus layer, exhibiting up to 1000 times the pull-off force of an unmodified microsphere, and showing greater adhesion than some chemical targeting means. In this paper, we demonstrate that nanotopography improves device adhesion in vivo, increasing retention time up to ten-fold over unmodified devices. Moreover, we observe considerable adhesion in several cell lines using an in vitro shear flow model, indicating that this approach is promising for numerous tissues. We then demonstrate that nanowire-mediated adhesion is highly robust to variation in nanowire surface charge and cellular structure and function, and we characterize particle loading and elution. We present a form of cytoadhesion that utilizes the physical interaction of nanoengineered surfaces with subcellular structures to produce a robust and versatile cytoadhesive for drug delivery. These nanoscale adhesive mechanisms are also relevant to fields such as tissue engineering and wound healing because they likely affect stem cell differentiation, cell remodeling, migration, etc.

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Transient cytochalasin-D treatment induces apically administered rAAV2 across tight junctions for transduction of enterocytes

Cited by 8 publications

References 26 publications

PEGylated silicon nanowire coated silica microparticles for drug delivery across intestinal epithelium

PEGylated silicon nanowire coated silica microparticles for drug delivery across intestinal epithelium

Rearrangement of Actin Cytoskeleton by Zika Virus Infection Facilitates Blood–Testis Barrier Hyperpermeability

Hierarchical nanoengineered surfaces for enhanced cytoadhesion and drug delivery

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