Disruption of the F-actin cytoskeleton and monolayer barrier integrity induced by PAF and the protective effect of ITF on intestinal epithelium

Xu, Liangliang; Xu, Cong; Mao, Zhi-Qin; Xu, Teng; Ma, Li; Sun, Mingzhe

doi:10.1007/s12272-011-0210-4

Cited by 19 publications

(17 citation statements)

References 38 publications

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“…28 F-actin and tight junction disruption has also been seen in intestinal epithelial cells. 29 We also observed that long-term PAF treatment (greater than 24 hours) reduced tight junction integrity. Although these responses are reversible by PAFR antagonists, such treatment may not be necessary as these exposures are longer than any intended in vitro or in vivo use.…”

Section: Discussionsupporting

confidence: 55%

“…As a mediator of inflammation, PAFR activation can alter tight junction integrity in endothelial and intestinal epithelial cells. 28,29 We examined the effects of PAF on tight junction integrity in airway epithelia. PAF application to the apical and basolateral surfaces of HAE for 8 hours caused no alteration of tight junction morphology as assessed by ZO-1 immunostaining.…”

Section: Resultsmentioning

confidence: 99%

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Platelet Activating Factor Receptor Activation Improves siRNA Uptake and RNAi Responses in Well-differentiated Airway Epithelia

Krishnamurthy

Behlke

Apicella

et al. 2014

Molecular Therapy - Nucleic Acids

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Well-differentiated human airway epithelia present formidable barriers to efficient siRNA delivery. We previously reported that treatment of airway epithelia with specific small molecules improves oligonucleotide uptake and facilitates RNAi responses. Here, we exploited the platelet activating factor receptor (PAFR) pathway, utilized by specific bacteria to transcytose into epithelia, as a trigger for internalization of Dicer-substrate siRNAs (DsiRNA). PAFR is a G-protein coupled receptor which can be engaged and activated by phosphorylcholine residues on the lipooligosaccharide (LOS) of nontypeable Haemophilus influenzae and the teichoic acid of Streptococcus pneumoniae as well as by its natural ligand, platelet activating factor (PAF). When well-differentiated airway epithelia were simultaneously treated with either nontypeable Haemophilus influenzae LOS or PAF and transduced with DsiRNA formulated with the peptide transductin, we observed silencing of both endogenous and exogenous targets. PAF receptor antagonists prevented LOS or PAF-assisted DsiRNA silencing, demonstrating that ligand engagement of PAFR is essential for this process. Additionally, PAF-assisted DsiRNA transfection decreased CFTR protein expression and function and reduced exogenous viral protein levels and titer in human airway epithelia. Treatment with spiperone, a small molecule identified using the Connectivity map database to correlate gene expression changes in response to drug treatment with those associated with PAFR stimulation, also induced silencing. These results suggest that the signaling pathway activated by PAFR binding can be manipulated to facilitate siRNA entry and function in difficult to transfect well-differentiated airway epithelial cells.

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Section: Discussionsupporting

confidence: 55%

Section: Resultsmentioning

confidence: 99%

Platelet Activating Factor Receptor Activation Improves siRNA Uptake and RNAi Responses in Well-differentiated Airway Epithelia

Krishnamurthy

Behlke

Apicella

et al. 2014

Molecular Therapy - Nucleic Acids

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“…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]. In general, the cytoskeletal pattern of actin molecules in the perijunctional region of intestinal epithelial cells tends to be either disrupted and modulated [27], or thickened and tightened [28] following incubation with particles or enteric biomolecules.…”

Section: Resultsmentioning

confidence: 80%

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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“…Similarly, all TFF peptides were shown in vitro in premalignant colonic epithelial cells to require activated Src/RhoA to induce cellular invasion (86, 87). Further support of TFF-mediated actin cytoskeleton rearrangement was demonstrated in the Caco-2 cells by Xu et al (88), who showed that TFF3 was capable of restricting platelet-activating factor-induced disruption of the F-actin cytoskeleton. These studies point to the role of TFF in activating actin cytoskeleton changes during cell migration.…”

Section: Trefoil Factor Peptides and Cell Migrationmentioning

confidence: 80%

Trefoil Factor Peptides and Gastrointestinal Function

Aihara

Engevik²,

Montrose³

2017

Annu. Rev. Physiol.

151

123

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Trefoil factor (TFF) peptides, containing a 40-amino acid motif, including six conserved cysteine residues that form intramolecular disulfide bonds, are a family of mucin-associated secretory molecules mediating many physiological roles that maintain and restore gastrointestinal (GI) mucosal homeostasis. TFF peptides play important roles in response to GI mucosal injury and inflammation. In response to acute GI mucosal injury, TFF peptides accelerate cell migration to seal the damaged area from luminal contents, whereas chronic inflammation leads to increased TFF expression to prevent further progression of disease. Although much evidence supports the physiological significance of TFF peptides in mucosal defenses, the molecular and cellular mechanisms of TFF peptides in the GI epithelium remain largely unknown. In this review, we summarize the functional roles of TFF1, 2, and 3 and illustrate their action mechanisms, focusing on defense mechanisms in the GI tract.

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Disruption of the F-actin cytoskeleton and monolayer barrier integrity induced by PAF and the protective effect of ITF on intestinal epithelium

Cited by 19 publications

References 38 publications

Platelet Activating Factor Receptor Activation Improves siRNA Uptake and RNAi Responses in Well-differentiated Airway Epithelia

Platelet Activating Factor Receptor Activation Improves siRNA Uptake and RNAi Responses in Well-differentiated Airway Epithelia

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

Trefoil Factor Peptides and Gastrointestinal Function

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