Molecular actors of the Calcium signaling in the endothelial-to-mesenchymal transition: poorly explored therapeutic targets
Abstract
Endothelial-to-mesenchymal transition (EndMT) is a cell trans-differentiation process which occurs during embryonic development as well as in a variety of pathological contexts. During this process, cells lose their endothelial lineage markers and gain mesenchymal ones. It is stimulated by several factors, such as TGF-β, high glucose, or hypoxia, which trigger intracellular pathways, mainly the Smad and ERK pathways, leading to modulation of transcription factors. While Ca 2+ signaling is known to participate in a wide variety of cellular processes, its role in the context of EndMT is only partially understood, although several Ca 2+ -carrying and Ca 2+regulated proteins have been shown to influence EndMT. These include Ca 2+ -permeable channels from the mechanosensitive Piezo family and members of the TRP family; the actors involved in store-operated Ca 2+ entry, including IP 3 -receptors located on the endoplasmic reticulum membrane, the endoplasmic reticulum Ca 2+ sensor STIM1, and the Ca 2+ -permeable plasma membrane channel Orai1; the mitochondrial Ca 2+ uniporter complex; Ca 2+ -activated channels such as the non-selective monovalent cation channel TRPM4 and the big-conductance K + channel BK Ca ; Ca 2+ -regulated signaling pathways such as the Ca 2+ -calmodulin-calcineurin-NFAT pathway and the calpain-ERK pathway.
After a brief description of Ca 2+ signaling in endothelial cells, this review will specifically detail the available data on the Ca 2+ signaling in EndMT. Links between Ca 2+ signaling and other signaling pathways leading to EndMT will be discussed. Finally, molecular targets that may be valuable to explore in order to prevent EndMT will be highlighted.
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BibTeX
@article{guinamard2026molecular,
title = {{Molecular actors of the Calcium signaling in the endothelial-to-mesenchymal transition: poorly explored therapeutic targets}},
author = {Romain Guinamard and Corentin Kerevel and Anaïs Darengosse and Valentin Platel and Laurent Sallé and Christophe Simard},
journal = {Cell Calcium},
year = {2026},
month = jun,
doi = {10.1016/j.ceca.2026.103163},
url = {https://hal.science/hal-05733195v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Molecular actors of the Calcium signaling in the endothelial-to-mesenchymal transition: poorly explored therapeutic targets
AU - Romain Guinamard
AU - Corentin Kerevel
AU - Anaïs Darengosse
AU - Valentin Platel
AU - Laurent Sallé
AU - Christophe Simard
PY - 2026
DA - 2026/06/25
JO - Cell Calcium
DO - 10.1016/j.ceca.2026.103163
UR - https://hal.science/hal-05733195v1
AB - Endothelial-to-mesenchymal transition (EndMT) is a cell trans-differentiation process which occurs during embryonic development as well as in a variety of pathological contexts. During this process, cells lose their endothelial lineage markers and gain mesenchymal ones. It is stimulated by several factors, such as TGF-β, high glucose, or hypoxia, which trigger intracellular pathways, mainly the Smad and ERK pathways, leading to modulation of transcription factors. While Ca 2+ signaling is known to participate in a wide variety of cellular processes, its role in the context of EndMT is only partially understood, although several Ca 2+ -carrying and Ca 2+regulated proteins have been shown to influence EndMT. These include Ca 2+ -permeable channels from the mechanosensitive Piezo family and members of the TRP family; the actors involved in store-operated Ca 2+ entry, including IP 3 -receptors located on the endoplasmic reticulum membrane, the endoplasmic reticulum Ca 2+ sensor STIM1, and the Ca 2+ -permeable plasma membrane channel Orai1; the mitochondrial Ca 2+ uniporter complex; Ca 2+ -activated channels such as the non-selective monovalent cation channel TRPM4 and the big-conductance K + channel BK Ca ; Ca 2+ -regulated signaling pathways such as the Ca 2+ -calmodulin-calcineurin-NFAT pathway and the calpain-ERK pathway. After a brief description of Ca 2+ signaling in endothelial cells, this review will specifically detail the available data on the Ca 2+ signaling in EndMT. Links between Ca 2+ signaling and other signaling pathways leading to EndMT will be discussed. Finally, molecular targets that may be valuable to explore in order to prevent EndMT will be highlighted.
SN - 0143-4160
SN - 1532-1991
ER -