Title: 1830 - Warm-activated TRPV4 Enhances Oral Epithelial Cell-cell Adhesion and Suppresses Migration
Reiko Yoshimoto (Presenter)
Reona Aijima, Saga University
Yasuyoshi Ohsaki, Kyushu University
Ailin Cao, Kyushu University
Jingqi Zhang, Kyushu University
Tamotsu Kiyoshima, Kyushu University
Fusanori Nishimura, Kyushu University
Mizuho Kido, Saga University
Objectives: Oral epithelia are dynamic tissues within the body that continually regenerate themselves with a proper barrier structure to resist thermal, chemical, and mechanical stimuli as well as bacterial infections in the oral cavity. We previously demonstrated that transient receptor potential channel vanilloid 4 (TRPV4), a thermosensitive and mechanosensitive Ca2+-permeable ion channel, is functionally expressed in oral epithelia. Here, we explored the role of TRPV4 in oral epithelial behavior providing the barrier function.
Methods: Palatal epithelia from TRPV4-deficient (V4KO) and wild-type (WT) mice were evaluated by calcium imaging, immunohistochemistry, and live-cell imaging. To understand the physiological function of TRPV4, we used a mouse model of palatal epithelial wound healing.
Results: Distinct TRPV4-immunoreactivities were found in the basal layer of the palatal epithelia. Isolated palatal epithelial cells showed TRPV4-dependent Ca2+ influx in response to increased temperature around 37°C. To examine the effects of temperature on the barrier function, primary oral epithelial cells were cultured at different temperatures. At 37°C, calcium stimulation led to intimate cell-cell contacts with linear E-cadherin staining in WT cells, while these effects were impaired in V4KO cells. By comparing cell cultures at 37°C and 31°C, temperature changes were found to regulate cell-cell contacts through the actomyosin cytoskeleton. Immunohistochemistry revealed an increased number of Ki67-positive proliferative cells within epithelia of V4KO mice compared with WT mice. Under live-cell imaging, V4KO cells exhibited higher migration than WT cells. Analyses of the mouse model of oral wound healing revealed accelerated healing in V4KO mice compared with WT mice.
Conclusions: The present findings suggest that TRPV4 facilitates cell-cell adhesion at warm temperatures in the oral cavity and regulates cellular proliferation and migration. TRPV4 may contribute to balancing of proper regeneration to provide the oral epithelial barrier.
This abstract is based on research that was funded entirely or partially by an outside source:
JSPS KAKENHI Grants JP16K15825 and JP16H05558 to M. A. K.
The submitter must disclose the names of the organizations with which any author have a relationship, the nature of the relationship, and the clinical or research area involved. The following is submitted: NONE