T-plastin expression downstream to the calcineurin/NFAT pathway is involved in keratinocyte migration.

Cutaneous wound healing requires keratinocyte proliferation, migration and differentiation to restore the barrier function of the skin. The calcineurin/nuclear factor of activated-T-cell (NFAT) signaling pathway has been recently shown to be involved in keratinocyte growth, differentiation and migra...

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Autores principales:	Cécilia Brun, Agathe Demeaux, Frédéric Guaddachi, Francette Jean-Louis, Thierry Oddos, Martine Bagot, Armand Bensussan, Sébastien Jauliac, Laurence Michel
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f8e9a5a1a9cd4f40b8a243827a193983
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spelling	oai:doaj.org-article:f8e9a5a1a9cd4f40b8a243827a1939832021-11-25T06:00:26ZT-plastin expression downstream to the calcineurin/NFAT pathway is involved in keratinocyte migration.1932-620310.1371/journal.pone.0104700https://doaj.org/article/f8e9a5a1a9cd4f40b8a243827a1939832014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0104700https://doaj.org/toc/1932-6203Cutaneous wound healing requires keratinocyte proliferation, migration and differentiation to restore the barrier function of the skin. The calcineurin/nuclear factor of activated-T-cell (NFAT) signaling pathway has been recently shown to be involved in keratinocyte growth, differentiation and migration. It is induced by an increased intracellular calcium rate and its inhibition results in decreased capacities of keratinocytes to migrate. Nevertheless, the link between calcineurin activation and keratinocyte migration remains unknown. Recently, Orai1, a pore subunit of a store-operated calcium channel that favors calcium influx, was shown to play a critical role to control proliferation and migration of basal keratinocytes. Of interest, the actin-bundling T-plastin is crucial in cell motility through cross-linking to actin filament and its synthesis was shown to be induced by calcium influx and regulated by the calcineurin/NFAT pathway in tumor Sezary cells. We investigated herein the role of the calcineurin/NFAT pathway-dependent T-plastin in keratinocyte migration, by quantifying T-plastin expression in keratinocytes and by analyzing their migration under calcineurin inhibition or knockdown of NFAT2 or T-plastin. We did confirm the role of the calcineurin/NFAT pathway in keratinocyte migration as shown by their decreased capacities to migrate after FK506 treatment or siNFAT2 transfection in both scratching and Boyden assays. The expression of NFAT2 and T-plastin in keratinocytes was decreased under FK506 treatment, suggesting that T-plastin plays a role in keratinocyte migration downstream to the calcineurin/NFAT pathway. Accordingly, siRNA knockdown of T-plastin expression also decreased their migration capacities. Actin lamellipodia formation as well as FAK and β6-integrin expression were also significantly decreased after treatment with FK506 or siRNA, reinforcing that NFAT2-dependent T-plastin expression plays a role in keratinocyte migration. These results indicate that T-plastin might be considered as a major actor in the mechanisms underlying calcineurin/NFAT-dependent keratinocyte migration and may explain wound-healing defects observed in patients under calcineurin inhibitor long-term treatment.Cécilia BrunAgathe DemeauxFrédéric GuaddachiFrancette Jean-LouisThierry OddosMartine BagotArmand BensussanSébastien JauliacLaurence MichelPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 9, p e104700 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Cécilia Brun Agathe Demeaux Frédéric Guaddachi Francette Jean-Louis Thierry Oddos Martine Bagot Armand Bensussan Sébastien Jauliac Laurence Michel T-plastin expression downstream to the calcineurin/NFAT pathway is involved in keratinocyte migration.
description	Cutaneous wound healing requires keratinocyte proliferation, migration and differentiation to restore the barrier function of the skin. The calcineurin/nuclear factor of activated-T-cell (NFAT) signaling pathway has been recently shown to be involved in keratinocyte growth, differentiation and migration. It is induced by an increased intracellular calcium rate and its inhibition results in decreased capacities of keratinocytes to migrate. Nevertheless, the link between calcineurin activation and keratinocyte migration remains unknown. Recently, Orai1, a pore subunit of a store-operated calcium channel that favors calcium influx, was shown to play a critical role to control proliferation and migration of basal keratinocytes. Of interest, the actin-bundling T-plastin is crucial in cell motility through cross-linking to actin filament and its synthesis was shown to be induced by calcium influx and regulated by the calcineurin/NFAT pathway in tumor Sezary cells. We investigated herein the role of the calcineurin/NFAT pathway-dependent T-plastin in keratinocyte migration, by quantifying T-plastin expression in keratinocytes and by analyzing their migration under calcineurin inhibition or knockdown of NFAT2 or T-plastin. We did confirm the role of the calcineurin/NFAT pathway in keratinocyte migration as shown by their decreased capacities to migrate after FK506 treatment or siNFAT2 transfection in both scratching and Boyden assays. The expression of NFAT2 and T-plastin in keratinocytes was decreased under FK506 treatment, suggesting that T-plastin plays a role in keratinocyte migration downstream to the calcineurin/NFAT pathway. Accordingly, siRNA knockdown of T-plastin expression also decreased their migration capacities. Actin lamellipodia formation as well as FAK and β6-integrin expression were also significantly decreased after treatment with FK506 or siRNA, reinforcing that NFAT2-dependent T-plastin expression plays a role in keratinocyte migration. These results indicate that T-plastin might be considered as a major actor in the mechanisms underlying calcineurin/NFAT-dependent keratinocyte migration and may explain wound-healing defects observed in patients under calcineurin inhibitor long-term treatment.
format	article
author	Cécilia Brun Agathe Demeaux Frédéric Guaddachi Francette Jean-Louis Thierry Oddos Martine Bagot Armand Bensussan Sébastien Jauliac Laurence Michel
author_facet	Cécilia Brun Agathe Demeaux Frédéric Guaddachi Francette Jean-Louis Thierry Oddos Martine Bagot Armand Bensussan Sébastien Jauliac Laurence Michel
author_sort	Cécilia Brun
title	T-plastin expression downstream to the calcineurin/NFAT pathway is involved in keratinocyte migration.
title_short	T-plastin expression downstream to the calcineurin/NFAT pathway is involved in keratinocyte migration.
title_full	T-plastin expression downstream to the calcineurin/NFAT pathway is involved in keratinocyte migration.
title_fullStr	T-plastin expression downstream to the calcineurin/NFAT pathway is involved in keratinocyte migration.
title_full_unstemmed	T-plastin expression downstream to the calcineurin/NFAT pathway is involved in keratinocyte migration.
title_sort	t-plastin expression downstream to the calcineurin/nfat pathway is involved in keratinocyte migration.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/f8e9a5a1a9cd4f40b8a243827a193983
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T-plastin expression downstream to the calcineurin/NFAT pathway is involved in keratinocyte migration.

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