NFAT5 controls the integrity of epidermis

Muhammad, Khalid; Xavier, Delicia; Klein-Hessling, Stefan; Azeem, Muhammad; Rauschenberger, Tabea; Murti, Krisna; Avots, Andris; Goebeler, Matthias; Klein, Matthias; Bopp, Tobias; Sielaff, Malte; Tenzer, Stefan; Möckel, Sigrid; Aramburu, José (Aramburu Beltrán); López Rodríguez, M. Cristina; Kerstan, Andreas; Serfling, Edgar

NFAT5 controls the integrity of epidermis

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dc.contributor.author Muhammad, Khalid
dc.contributor.author Xavier, Delicia
dc.contributor.author Klein-Hessling, Stefan
dc.contributor.author Azeem, Muhammad
dc.contributor.author Rauschenberger, Tabea
dc.contributor.author Murti, Krisna
dc.contributor.author Avots, Andris
dc.contributor.author Goebeler, Matthias
dc.contributor.author Klein, Matthias
dc.contributor.author Bopp, Tobias
dc.contributor.author Sielaff, Malte
dc.contributor.author Tenzer, Stefan
dc.contributor.author Möckel, Sigrid
dc.contributor.author Aramburu, José (Aramburu Beltrán)
dc.contributor.author López Rodríguez, M. Cristina
dc.contributor.author Kerstan, Andreas
dc.contributor.author Serfling, Edgar
dc.date.accessioned 2022-02-15T06:47:05Z
dc.date.available 2022-02-15T06:47:05Z
dc.date.issued 2021
dc.description.abstract The skin protects the human body against dehydration and harmful challenges. Keratinocytes (KCs) are the most abundant epidermal cells, and it is anticipated that KC-mediated transport of Na+ ions creates a physiological barrier of high osmolality against the external environment. Here, we studied the role of NFAT5, a transcription factor whose activity is controlled by osmotic stress in KCs. Cultured KCs from adult mice were found to secrete more than 300 proteins, and upon NFAT5 ablation, the secretion of several matrix proteinases, including metalloproteinase-3 (Mmp3) and kallikrein-related peptidase 7 (Klk7), was markedly enhanced. An increase in Mmp3 and Klk7 RNA levels was also detected in transcriptomes of Nfat5-/- KCs, along with increases of numerous members of the 'Epidermal Differentiation Complex' (EDC), such as small proline-rich (Sprr) and S100 proteins. NFAT5 and Mmp3 as well as NFAT5 and Klk7 are co-expressed in the basal KCs of fetal and adult epidermis but not in basal KCs of newborn (NB) mice. The poor NFAT5 expression in NB KCs is correlated with a strong increase in Mmp3 and Klk7 expression in KCs of NB mice. These data suggests that, along with the fragile epidermis of adult Nfat5-/- mice, NFAT5 keeps in check the expression of matrix proteases in epidermis. The NFAT5-mediated control of matrix proteases in epidermis contributes to the manifold changes in skin development in embryos before and during birth, and to the integrity of epidermis in adults.
dc.format.mimetype application/pdf
dc.identifier.citation Muhammad K, Xavier D, Klein-Hessling S, Azeem M, Rauschenberger T, Murti K, Avots A, Goebeler M, Klein M, Bopp T, Sielaff M, Tenzer S, Möckel S, Aramburu J, López-Rodríguez C, Kerstan A, Serfling E. NFAT5 controls the integrity of epidermis. Front Immunol. 2021;12:780727. DOI: 10.3389/fimmu.2021.780727
dc.identifier.doi http://dx.doi.org/10.3389/fimmu.2021.780727
dc.identifier.issn 1664-3224
dc.identifier.uri http://hdl.handle.net/10230/52489
dc.language.iso eng
dc.publisher Frontiers
dc.relation.ispartof Front Immunol. 2021;12:780727
dc.rights © 2021 Muhammad, Xavier, Klein-Hessling, Azeem, Rauschenberger, Murti, Avots, Goebeler, Klein, Bopp, Sielaff, Tenzer, Möckel, Aramburu, López-Rodríguez, Kerstan and Serfling. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.keyword Mmp3
dc.subject.keyword NFAT5
dc.subject.keyword Epidermis
dc.subject.keyword Kallikrein 7
dc.subject.keyword Keratinocytes
dc.subject.keyword Matrix proteases
dc.subject.keyword Skin
dc.title NFAT5 controls the integrity of epidermis
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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