Nerve Growth Factor Modulates Regulatory Cell Volume Behavior via Stimulating TRPV1, TRPM8 Channels and Inducing Ca<sup>2+</sup> Signaling in Human Conjunctival Epithelial Cells

NGF plays important roles in ocular surface homeostasis and different pathological conditions. One effect includes promoting conjunctival epithelial cell differentiation and mucin secretion. This study characterizes the individual roles of TRPV1 and TRPM8 channel activity in mediating the effects of...

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Main Authors: Friedrich Wolf, Tina Dietrich-Ntoukas, Peter S. Reinach, Uwe Pleyer, Stefan Mergler
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/14/10/719
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author Friedrich Wolf
Tina Dietrich-Ntoukas
Peter S. Reinach
Uwe Pleyer
Stefan Mergler
author_facet Friedrich Wolf
Tina Dietrich-Ntoukas
Peter S. Reinach
Uwe Pleyer
Stefan Mergler
author_sort Friedrich Wolf
collection DOAJ
description NGF plays important roles in ocular surface homeostasis and different pathological conditions. One effect includes promoting conjunctival epithelial cell differentiation and mucin secretion. This study characterizes the individual roles of TRPV1 and TRPM8 channel activity in mediating the effects of NGF on intracellular Ca<sup>2+</sup> regulation and its alteration of regulatory cell volume responses to anisosmotic challenges in human conjunctival epithelial cells (IOBA-NHC). With fura-2/AM-loaded cells, the effects of 40 µM capsaicin and 20 µM AMG 9810 on Ca<sup>2+</sup> regulation confirm functional TRPV1 expression. TRPM8 expression is evident since 500 µM menthol and 20 µM AMTB have opposing effects on [Ca<sup>2+</sup>]<sub>i</sub>. AMG 9810 and AMTB (both 20 µM) suppress the responses to NGF (100 ng/mL). With calcein/AM-loaded cells, the effects of these mediators are evaluated on apparent cell volume responses induced by an anisosmotic challenge. NGF decreases the apparent cell volume that AMG 9810 suppresses, whereas AMTB (both 20 µM) augments this response. Therefore, NGF interacts with TRPV1 and TRPM8 to induce opposing effects on cell volume regulatory behavior. These opposing effects suggest that the signaling pathways and effectors that mediate responses to TRPV1 and TRPM8 activation are not the same.
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spelling doaj-art-9f4be9f7e7574175b23a450569dba9c02025-08-20T02:33:38ZengMDPI AGCells2073-44092025-05-01141071910.3390/cells14100719Nerve Growth Factor Modulates Regulatory Cell Volume Behavior via Stimulating TRPV1, TRPM8 Channels and Inducing Ca<sup>2+</sup> Signaling in Human Conjunctival Epithelial CellsFriedrich Wolf0Tina Dietrich-Ntoukas1Peter S. Reinach2Uwe Pleyer3Stefan Mergler4Department of Ophthalmology, Charité—Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, GermanyDepartment of Ophthalmology, Charité—Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, GermanySchool of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou 325015, ChinaDepartment of Ophthalmology, Charité—Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, GermanyDepartment of Ophthalmology, Charité—Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, GermanyNGF plays important roles in ocular surface homeostasis and different pathological conditions. One effect includes promoting conjunctival epithelial cell differentiation and mucin secretion. This study characterizes the individual roles of TRPV1 and TRPM8 channel activity in mediating the effects of NGF on intracellular Ca<sup>2+</sup> regulation and its alteration of regulatory cell volume responses to anisosmotic challenges in human conjunctival epithelial cells (IOBA-NHC). With fura-2/AM-loaded cells, the effects of 40 µM capsaicin and 20 µM AMG 9810 on Ca<sup>2+</sup> regulation confirm functional TRPV1 expression. TRPM8 expression is evident since 500 µM menthol and 20 µM AMTB have opposing effects on [Ca<sup>2+</sup>]<sub>i</sub>. AMG 9810 and AMTB (both 20 µM) suppress the responses to NGF (100 ng/mL). With calcein/AM-loaded cells, the effects of these mediators are evaluated on apparent cell volume responses induced by an anisosmotic challenge. NGF decreases the apparent cell volume that AMG 9810 suppresses, whereas AMTB (both 20 µM) augments this response. Therefore, NGF interacts with TRPV1 and TRPM8 to induce opposing effects on cell volume regulatory behavior. These opposing effects suggest that the signaling pathways and effectors that mediate responses to TRPV1 and TRPM8 activation are not the same.https://www.mdpi.com/2073-4409/14/10/719nerve growth factorTRPV 1TRPM 8conjunctival epithelial cellsCa<sup>2+</sup> regulation
spellingShingle Friedrich Wolf
Tina Dietrich-Ntoukas
Peter S. Reinach
Uwe Pleyer
Stefan Mergler
Nerve Growth Factor Modulates Regulatory Cell Volume Behavior via Stimulating TRPV1, TRPM8 Channels and Inducing Ca<sup>2+</sup> Signaling in Human Conjunctival Epithelial Cells
Cells
nerve growth factor
TRPV 1
TRPM 8
conjunctival epithelial cells
Ca<sup>2+</sup> regulation
title Nerve Growth Factor Modulates Regulatory Cell Volume Behavior via Stimulating TRPV1, TRPM8 Channels and Inducing Ca<sup>2+</sup> Signaling in Human Conjunctival Epithelial Cells
title_full Nerve Growth Factor Modulates Regulatory Cell Volume Behavior via Stimulating TRPV1, TRPM8 Channels and Inducing Ca<sup>2+</sup> Signaling in Human Conjunctival Epithelial Cells
title_fullStr Nerve Growth Factor Modulates Regulatory Cell Volume Behavior via Stimulating TRPV1, TRPM8 Channels and Inducing Ca<sup>2+</sup> Signaling in Human Conjunctival Epithelial Cells
title_full_unstemmed Nerve Growth Factor Modulates Regulatory Cell Volume Behavior via Stimulating TRPV1, TRPM8 Channels and Inducing Ca<sup>2+</sup> Signaling in Human Conjunctival Epithelial Cells
title_short Nerve Growth Factor Modulates Regulatory Cell Volume Behavior via Stimulating TRPV1, TRPM8 Channels and Inducing Ca<sup>2+</sup> Signaling in Human Conjunctival Epithelial Cells
title_sort nerve growth factor modulates regulatory cell volume behavior via stimulating trpv1 trpm8 channels and inducing ca sup 2 sup signaling in human conjunctival epithelial cells
topic nerve growth factor
TRPV 1
TRPM 8
conjunctival epithelial cells
Ca<sup>2+</sup> regulation
url https://www.mdpi.com/2073-4409/14/10/719
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