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Digestive Diseases and Sciences

Erschienen in:

01.12.2015 | Original Article

Protease-Activated Receptor-2 Up-Regulates Transient Receptor Potential Vanilloid 4 Function in Mouse Esophageal Keratinocyte

verfasst von: Nobuhiro Suzuki, Hiroshi Mihara, Hirofumi Nishizono, Makoto Tominaga, Toshiro Sugiyama

Erschienen in: Digestive Diseases and Sciences | Ausgabe 12/2015

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Abstract

Background

The reflux of pancreatic–duodenal fluids is implicated in the pathophysiology of proton-pump inhibitor-resistant gastroesophageal reflux disease (GERD). Protease-activated receptor-2 (PAR-2) is activated by proteases, the pancreatic enzyme, trypsin, and the activated PAR-2 enhances transient receptor potential vanilloid 4 (TRPV4) function in neurons. TRPV4 stimulates ATP exocytosis in conjunction with the vesicular nucleotide transporter, which mediates mechano-transduction and vagal stimulation. The aim of the present study was to verify whether the activated PAR-2 up-regulates TRPV4 function in mouse esophageal keratinocytes, which may link to the pathophysiology in PPI-resistant GERD.

Methods

TRPV4 and PAR-2 expressions were detected by RT-PCR, immunostaining, and western blotting in mouse esophageal keratinocytes. The functional response of TRPV4 to esophageal keratinocytes was analyzed using a Ca²⁺ imaging system. Cellular ATP release was examined by luciferase–luciferin reaction. TRPV4 phosphorylation was studied by immunoprecipitation and western blotting.

Results

PAR-2 and TRPV4 mRNAs and proteins were expressed in esophageal keratinocytes. Pre-treatment with trypsin significantly increased the responses to TRPV4 activator in esophageal keratinocytes, probably via the phosphorylation of serine residue of TRPV4 by protein kinase C and resulted in cellular ATP release from the cells.

Conclusions

Activated PAR-2 with trypsin exposure up-regulated TRPV4 function and increased ATP release in mouse esophageal keratinocytes. This mechanism might be related to the pathophysiology of GERD, especially non-erosive GERD.

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Titel: Protease-Activated Receptor-2 Up-Regulates Transient Receptor Potential Vanilloid 4 Function in Mouse Esophageal Keratinocyte
verfasst von: Nobuhiro Suzuki
Hiroshi Mihara
Hirofumi Nishizono
Makoto Tominaga
Toshiro Sugiyama
Publikationsdatum: 01.12.2015
Verlag: Springer US
Erschienen in: Digestive Diseases and Sciences / Ausgabe 12/2015
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-015-3822-6

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Abstract

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