Deletion of TRPV4 enhances in vitro wound healing of murine esophageal keratinocytes

Ammar Boudaka,Claire T Saito,Makoto Tominaga

doi:10.1038/s41598-020-68269-8

Abstract

Transient receptor potential vanilloid 4 (TRPV4) is a non-selective cation channel that is widely expressed in different body tissues and plays several physiological roles. This channel is highly expressed in esophageal keratinocytes where its activation mediates ATP release. However, whether TRPV4 has a role in wound healing of esophageal keratinocytes is unclear. In this study, we demonstrated that both cell migration and proliferation were slower in wild-type esophageal keratinocytes compared to cells having TRPV4 knockout. Our results suggest that TRPV4-mediated release of ATP from esophageal keratinocytes contributes to a decrease in the rate of in vitro wound healing via the ATP degradation product adenosine, which acts on A2B adenosine receptors.

Highlights

Transient receptor potential vanilloid 4 (TRPV4) is a non-selective cation channel that is widely expressed in different body tissues and plays several physiological roles
Our results indicate that TRPV4-mediated ATP release from esophageal keratinocytes slows in vitro wound healing via a degradation product of ATP, adenosine, which acts on A2B adenosine receptors
The wound healing assay revealed that the percentages of covered gap area were significantly larger for TRPV4-KO compared to WT esophageal keratinocytes at both 48 and 72 h after insert removal (48 h: 54.5 ± 4.9% vs. 26.7 ± 2.1%; 72 h: 84.0 ± 2.8% vs. 48.8 ± 2.8%; n = 18–24; p < 0.01) (Fig. 1a,b)

Summary

Introduction

Transient receptor potential vanilloid 4 (TRPV4) is a non-selective cation channel that is widely expressed in different body tissues and plays several physiological roles. This channel is highly expressed in esophageal keratinocytes where its activation mediates ATP release. Mucolipin (TRPML1-3), poly-cystin (PC) (TRPP1-3), and vanilloid (TRPV1-6)[5,8,9] These channels are generally expressed in various body tissues and many cells express one or more subtypes. TRP channel activation can be achieved by a large array of physical and chemical stimuli including mechanical forces, heat, cold, ions and small molecules[15,16]. TRP channels are crucial players in multiple facets of health and disease[17]

Methods

Results

Conclusion