Transient receptor potential A1 channels regulate epithelial cell barriers formed by <scp>MDCK</scp> cells

Dembla, Sandeep; Hasan, Nouma; Becker, Alexander; Beck, Andreas; Philipp, Stephan E.

doi:10.1002/1873-3468.12183

Cited by 10 publications

(8 citation statements)

References 62 publications

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“…6C , lower graph). These results suggest that AITC can increase the TJ permeability via TRPA1 activation, corresponding with the previous finding that 100 μM AITC reduced the TER of MDCK II cell layers 33 .…”

Section: Resultssupporting

confidence: 91%

“…Earlier studies showed that structurally unrelated electrophilic compounds activated TRPA1 through the covalent modification of cysteine residues 30 – 32 . In addition, it was recently reported that the TRPA1 agonist allyisothiocyanate (AITC) reduced the TER of MDCK II cell layers, offering the TRPA1 channel as a regulator of epithelial cell barriers 33 . It is also noteworthy that the non-pungent capsaicin analog capsiate activates TRPA1 34 .…”

Section: Resultsmentioning

confidence: 99%

“…A cation channel, TRPA1, is known to be activated by structurally unrelated electrophiles through the modification of cysteine residues within the cytoplasmic N terminus of the channel 30 , 31 . It was recently demonstrated that MDCK II cells express TRPA1, contributing to Ca 2+ influx and TJ regulation 33 . As speculated, here we observed that compound 2 activates TRPA1 to induce a Ca 2+ influx and TJ permeability increase.…”

Section: Discussionmentioning

confidence: 99%

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TRPA1-dependent reversible opening of tight junction by natural compounds with an α,β-unsaturated moiety and capsaicin

Kanda

Yamasaki

Sasaki-Yamaguchi

et al. 2018

Sci Rep

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The delivery of hydrophilic macromolecules runs into difficulties such as penetration of the cell membrane lipid bilayer. Our prior experiment demonstrated that capsaicin induces the reversible opening of tight junctions (TJs) and enhances the delivery of hydrophilic macromolecules through a paracellular route. Herein, we screened paracellular permeability enhancers other than capsaicin. As TJ opening by capsaicin is associated with Ca2+ influx, we first screened the compounds that induce Ca2+ influx in layered MDCK II cells, and then we determined the compounds’ abilities to open TJs. Our results identified several natural compounds with α,β-unsaturated moiety. A structure-activity relationship (SAR) analysis and the results of pretreatment with reducing reagent DTT suggested the importance of α,β-unsaturated moiety. We also examined the underlying mechanisms, and our findings suggest that the actin reorganization seen in capsaicin treatment is important for the reversibility of TJ opening. Furthermore, our analyses revealed that TRPA1 is involved in the Ca2+ influx and TJ permeability increase not only by an α,β-unsaturated compound but also by capsaicin. Our results indicate that the α,β-unsaturated moiety can be a potent pharmacophore for TJ opening.

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Section: Resultssupporting

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

TRPA1-dependent reversible opening of tight junction by natural compounds with an α,β-unsaturated moiety and capsaicin

Kanda

Yamasaki

Sasaki-Yamaguchi

et al. 2018

Sci Rep

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“…Once maximum confluence is achieved, contact inhibition and tight junction remodeling takes place, which leads to a decrease in the TER that eventually stabilizes and becomes constant as the cells form stable mature tight junctions [32,33]. In MDCK II cells, this translated into a decrease in TER that then remained at 50–80 Ω·cm 2 , which is characteristic for mature tight junctions in this model [33]. Therefore, this was the time point selected for treatment with quercetin since it best represents the mature renal proximal tubule epithelium.…”

Section: Resultsmentioning

confidence: 99%

Temporal Effects of Quercetin on Tight Junction Barrier Properties and Claudin Expression and Localization in MDCK II Cells

Gamero-Estevez

Andonian

Jean‐Claude

et al. 2019

IJMS

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Kidney stones affect 10% of the population. Yet, there is relatively little known about how they form or how to prevent and treat them. The claudin family of tight junction proteins has been linked to the formation of kidney stones. The flavonoid quercetin has been shown to prevent kidney stone formation and to modify claudin expression in different models. Here we investigate the effect of quercetin on claudin expression and localization in MDCK II cells, a cation-selective cell line, derived from the proximal tubule. For this study, we focused our analyses on claudin family members that confer different tight junction properties: barrier-sealing (Cldn1, -3, and -7), cation-selective (Cldn2) or anion-selective (Cldn4). Our data revealed that quercetin’s effects on the expression and localization of different claudins over time corresponded with changes in transepithelial resistance, which was measured continuously throughout the treatment. In addition, these effects appear to be independent of PI3K/AKT signaling, one of the pathways that is known to act downstream of quercetin. In conclusion, our data suggest that quercetin’s effects on claudins result in a tighter epithelial barrier, which may reduce the reabsorption of sodium, calcium and water, thereby preventing the formation of a kidney stone.

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“…Neuronal TRPA1 acts as a sensor of toxic signals and molecular integrator of cellular stress, including ROS [20,21]. Recent studies have demonstrated that TRPA1 is expressed in various types of non-neuronal cells, including renal epithelial tubular cells [22,23]. Promoting inflammation is among the major functions of TRPA1 in non-neuronal cells [24].…”

Section: Introductionmentioning

confidence: 99%

Renal Tubular Epithelial TRPA1 Acts as An Oxidative Stress Sensor to Mediate Ischemia-Reperfusion-Induced Kidney Injury through MAPKs/NF-κB Signaling

Lee

et al. 2021

IJMS

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Oxidative stress and inflammation play important roles in the pathophysiology of acute kidney injury (AKI). Transient receptor potential ankyrin 1 (TRPA1) is a Ca2+-permeable ion channel that is sensitive to reactive oxygen species (ROS). The role of TRPA1 in AKI remains unclear. In this study, we used human and animal studies to assess the role of renal TRPA1 in AKI and to explore the regulatory mechanism of renal TRPA1 in inflammation via in vitro experiments. TRPA1 expression increased in the renal tubular epithelia of patients with AKI. The severity of tubular injury correlated well with tubular TRPA1 or 8-hydroxy-2′-deoxyguanosine expression. In an animal model, renal ischemia-reperfusion injury (IR) increased tubular TRPA1 expression in wild-type (WT) mice. Trpa1−/− mice displayed less IR-induced tubular injury, oxidative stress, inflammation, and dysfunction in kidneys compared with WT mice. In the in vitro model, TRPA1 expression increased in renal tubular cells under hypoxia-reoxygenation injury (H/R) conditions. We demonstrated that H/R evoked a ROS-dependent TRPA1 activation, which elevated intracellular Ca2+ level, increased NADPH oxidase activity, activated MAPK/NF-kB signaling, and increased IL-8. Renal tubular TRPA1 may serve as an oxidative stress sensor and a crucial regulator in the activation of signaling pathways and promote the subsequent transcriptional regulation of IL-8. These actions might be evident in mice with IR or patients with AKI.

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Transient receptor potential A1 channels regulate epithelial cell barriers formed by MDCK cells

Cited by 10 publications

References 62 publications

TRPA1-dependent reversible opening of tight junction by natural compounds with an α,β-unsaturated moiety and capsaicin

TRPA1-dependent reversible opening of tight junction by natural compounds with an α,β-unsaturated moiety and capsaicin

Temporal Effects of Quercetin on Tight Junction Barrier Properties and Claudin Expression and Localization in MDCK II Cells

Renal Tubular Epithelial TRPA1 Acts as An Oxidative Stress Sensor to Mediate Ischemia-Reperfusion-Induced Kidney Injury through MAPKs/NF-κB Signaling

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