Vascular Endothelial Growth Factor (VEGF) Induced Downstream Responses to Transient Receptor Potential Vanilloid 1 (TRPV1) and 3-Iodothyronamine (3-T1AM) in Human Corneal Keratocytes

Tuerker E, Garreis F, Khajavi N, Reinach PS, Joshi P, Brockmann T, Lucius A, Ljubojevic N, Turan E, Cooper D, Schick F, Reinholz R, Pleyer U, Koehrle J, Mergler S (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Frontiers in Endocrinology Frontiers Media

Book Volume: 9

DOI: 10.3389/fendo.2018.00670

Abstract

This study was undertaken to determine if crosstalk among the transient receptor potential (TRP) melastatin 8 (TRPM8), TRP vanilloid 1 (TRPV1), and vascular endothelial growth factor (VEGF) receptor triad modulates VEGF-induced Ca2+ signaling in human corneal keratocytes. Using RT-PCR, qPCR and immunohistochemistry, we determined TRPV1 and TRPM8 gene and protein coexpression in a human corneal keratocyte cell line (HCK) and human corneal cross sections. Fluorescence Ca2+ imaging using both a photomultiplier and a single cell digital imaging system as well as planar patch-clamping measured relative intracellular Ca2+ levels and underlying whole-cell currents. The TRPV1 agonist capsaicin increased both intracellular Ca2+ levels and whole-cell currents, while the antagonist capsazepine (CPZ) inhibited them. VEGF-induced Ca2+ transients and rises in whole-cell currents were suppressed by CPZ, whereas a selective TRPM8 antagonist, AMTB, increased VEGF signaling. In contrast, an endogenous thyroid hormone-derived metabolite 3-Iodothyronamine (3-T1AM) suppressed increases in the VEGF-induced current. The TRPM8 agonist menthol increased the currents, while AMTB suppressed this response. The VEGF-induced increases in Ca2+ influx and their underlying ionic currents stem from crosstalk between VEGFR and TRPV1, which can be impeded by 3-T1AM-induced TRPM8 activation. Such suppression in turn blocks VEGF-induced TRPV1 activation. Therefore, crosstalk between TRPM8 and TRPV1 inhibits VEGFR-induced activation of TRPV1.

Authors with CRIS profile

Fabian Garreis Lehrstuhl für Funktionelle und Klinische Anatomie

Involved external institutions

Charité - Universitätsmedizin Berlin DE Germany (DE) Freie Universität Berlin DE Germany (DE) Wenzhou Medical University / 温州医科大学 (WMU) CN China (CN)

How to cite

APA:

Tuerker, E., Garreis, F., Khajavi, N., Reinach, P.S., Joshi, P., Brockmann, T.,... Mergler, S. (2018). Vascular Endothelial Growth Factor (VEGF) Induced Downstream Responses to Transient Receptor Potential Vanilloid 1 (TRPV1) and 3-Iodothyronamine (3-T1AM) in Human Corneal Keratocytes. Frontiers in Endocrinology, 9. https://doi.org/10.3389/fendo.2018.00670

MLA:

Tuerker, Ersal, et al. "Vascular Endothelial Growth Factor (VEGF) Induced Downstream Responses to Transient Receptor Potential Vanilloid 1 (TRPV1) and 3-Iodothyronamine (3-T1AM) in Human Corneal Keratocytes." Frontiers in Endocrinology 9 (2018).

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