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Open AccessArticle

TRPM6 is Essential for Magnesium Uptake and Epithelial Cell Function in the Colon

1
Istituto di Patologia Generale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, I-00168 Rome, Italy
2
Laboratoire de Physiologie Cellulaire et Moléculaire-EA4667, UFR Sciences, Université de Picardie Jules Verne, F-80039 Amiens, France
*
Authors to whom correspondence should be addressed.
Nutrients 2018, 10(6), 784; https://doi.org/10.3390/nu10060784
Received: 28 May 2018 / Revised: 12 June 2018 / Accepted: 13 June 2018 / Published: 18 June 2018
(This article belongs to the Special Issue Magnesium Intake and Human Health)
Intestinal magnesium (Mg) uptake is essential for systemic Mg homeostasis. Colon cells express the two highly homologous transient receptor potential melastatin type (TRPM) 6 and 7 Mg2+ channels, but their precise function and the consequences of their mutual interaction are not clear. To explore the functional role of TRPM6 and TRPM7 in the colon, we used human colon cell lines that innately express both channels and analyzed the functional consequences of genetic knocking-down, by RNA interference, or pharmacological inhibition, by NS8593, of either channel. TRPM7 silencing caused an increase in Mg2+ influx, and correspondingly enhanced cell proliferation and migration, while downregulation of TRPM6 did not affect significantly either Mg2+ influx or cell proliferation. Exposure to the specific TRPM6/7 inhibitor NS8593 reduced Mg2+ influx, and consequently cell proliferation and migration, but Mg supplementation rescued the inhibition. We propose a model whereby in colon cells the functional Mg2+ channel at the plasma membrane may consist of both TRPM7 homomers and TRPM6/7 heteromers. A different expression ratio between the two proteins may result in different functional properties. Altogether, our findings confirm that TRPM6 cannot be replaced by TRPM7, and that TRPM6/7 complexes and TRPM6/7-mediated Mg2+ influx are indispensable in human epithelial colon cells. View Full-Text
Keywords: cell migration; cell proliferation; intestine; ion imaging; magnesium channel; magnesium homeostasis; MagT1; NS8593; TRPM7; wound healing cell migration; cell proliferation; intestine; ion imaging; magnesium channel; magnesium homeostasis; MagT1; NS8593; TRPM7; wound healing
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Luongo, F.; Pietropaolo, G.; Gautier, M.; Dhennin-Duthille, I.; Ouadid-Ahidouch, H.; Wolf, F.I.; Trapani, V. TRPM6 is Essential for Magnesium Uptake and Epithelial Cell Function in the Colon. Nutrients 2018, 10, 784.

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