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1.
Biosci Biotechnol Biochem ; 88(1): 44-52, 2023 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-37838472

RESUMEN

Capsaicin induces the reversible opening of tight junctions (TJs) and enhances the delivery of hydrophilic macromolecules through a paracellular route. We previously revealed that TRPA1 is involved in the capsaicin-induced Ca2+ influx and TJ permeability increase, although there are no reports that capsaicin directly activates TRPA1. In this study, we investigated the upstream factors of TRPA1 using RNA-seq analysis, and found that the cyclooxygenase 2 (COX2) gene was upregulated by capsaicin. Cyclooxygenase 2 converts arachidonic acid (AA), a metabolite by phospholipase A2 (PLA2), to prostaglandins. Prostaglandin E2 (PGE2) production was stimulated by capsaicin, and capsaicin-induced Ca2+ influx was effectively inhibited by PLA2 and COX2 inhibitors. The AA-induced TJ permeability increase was inhibited by a TRPA1 antagonist, but the capsaicin- and AA-induced TJ permeability increases were hardly inhibited by a COX2 inhibitor. These results suggest that capsaicin-induced PLA2 activation and AA production are the important steps for the TJ permeability increase.


Asunto(s)
Calcio , Capsaicina , Ácido Araquidónico/farmacología , Ácido Araquidónico/metabolismo , Capsaicina/farmacología , Ciclooxigenasa 2/genética , Calcio/metabolismo , Fosfolipasas A2
2.
Stud Health Technol Inform ; 264: 1596-1597, 2019 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-31438249

RESUMEN

Nephrosis is disease characterized by abnormal protein loss from impaired kidney. We constructed early prediction model using machine learning from clinical time series data, that can predict onset of nephrosis for more than one month. Long short-term memory capable of recognizing temporal sequential data patterns, was adopted as early prediction model for nephrosis. We verified our proposed prediction model has higher accuracy compared with those of baseline classifiers by 5-fold cross validation.


Asunto(s)
Aprendizaje Profundo , Nefrosis , Diagnóstico Precoz , Humanos , Aprendizaje Automático , Nefrosis/diagnóstico
3.
FEBS Lett ; 593(16): 2250-2260, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31206656

RESUMEN

The transient receptor potential V4 channel (TRPV4) is responsive to a variety of physical and chemical stimuli, including a synthetic agonist GSK1016790A (GSK). Here, we show that TRPV4 is functionally expressed in, and that GSK induces the reversible opening of tight junctions (TJs) in epithelial Madin-Darby canine kidney II monolayers. Stimulation of TRPV4 by GSK induces an increase in fluorescein isothiocyanate-conjugated dextran (4 kDa) permeability and a reduction in transepithelial resistance, and these responses are blocked by pretreatment with the specific TRPV4 antagonist. Small conductance, but not large conductance Ca2+ -activated K+ channels, TRPA1 channel, and cofilin activation are involved in TRPV4-mediated reversible opening of TJs. These results suggest that a novel mechanism underlies TRPV4-mediated regulation of the tightness of epithelial barriers.


Asunto(s)
Células Epiteliales/citología , Leucina/análogos & derivados , Sulfonamidas/farmacología , Canales Catiónicos TRPV/metabolismo , Uniones Estrechas/metabolismo , Factores Despolimerizantes de la Actina/metabolismo , Animales , Permeabilidad de la Membrana Celular/efectos de los fármacos , Perros , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Leucina/farmacología , Células de Riñón Canino Madin Darby , Canal Catiónico TRPA1/metabolismo , Uniones Estrechas/efectos de los fármacos
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