Cargando…

Latent TGF-β Activation Is a Hallmark of the Tenascin Family

Transforming growth factor-β (TGF-β) isoforms are secreted as inactive complexes formed through non-covalent interactions between bioactive TGF-β entities and their N-terminal pro-domains called latency-associated peptides (LAP). Extracellular activation of latent TGF-β within this complex is a cruc...

Descripción completa

Detalles Bibliográficos
Autores principales: Aubert, Alexandre, Mercier-Gouy, Perrine, Aguero, Stéphanie, Berthier, Laurent, Liot, Sophie, Prigent, Laura, Alcaraz, Lindsay B., Verrier, Bernard, Terreux, Raphaël, Moali, Catherine, Lambert, Elise, Valcourt, Ulrich
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155481/
https://www.ncbi.nlm.nih.gov/pubmed/34054795
http://dx.doi.org/10.3389/fimmu.2021.613438
_version_ 1783699213524140032
author Aubert, Alexandre
Mercier-Gouy, Perrine
Aguero, Stéphanie
Berthier, Laurent
Liot, Sophie
Prigent, Laura
Alcaraz, Lindsay B.
Verrier, Bernard
Terreux, Raphaël
Moali, Catherine
Lambert, Elise
Valcourt, Ulrich
author_facet Aubert, Alexandre
Mercier-Gouy, Perrine
Aguero, Stéphanie
Berthier, Laurent
Liot, Sophie
Prigent, Laura
Alcaraz, Lindsay B.
Verrier, Bernard
Terreux, Raphaël
Moali, Catherine
Lambert, Elise
Valcourt, Ulrich
author_sort Aubert, Alexandre
collection PubMed
description Transforming growth factor-β (TGF-β) isoforms are secreted as inactive complexes formed through non-covalent interactions between bioactive TGF-β entities and their N-terminal pro-domains called latency-associated peptides (LAP). Extracellular activation of latent TGF-β within this complex is a crucial step in the regulation of TGF-β activity for tissue homeostasis and immune cell function. We previously showed that the matrix glycoprotein Tenascin-X (TN-X) interacted with the small latent TGF-β complex and triggered the activation of the latent cytokine into a bioactive TGF-β. This activation most likely occurs through a conformational change within the latent TGF-β complex and requires the C-terminal fibrinogen-like (FBG) domain of the glycoprotein. As the FBG-like domain is highly conserved among the Tenascin family members, we hypothesized that Tenascin-C (TN-C), Tenascin-R (TN-R) and Tenascin-W (TN-W) might share with TN-X the ability to regulate TGF-β bioavailability through their C-terminal domain. Here, we demonstrate that purified recombinant full-length Tenascins associate with the small latent TGF-β complex through their FBG-like domains. This association promotes activation of the latent cytokine and subsequent TGF-β cell responses in mammary epithelial cells, such as cytostasis and epithelial-to-mesenchymal transition (EMT). Considering the pleiotropic role of TGF-β in numerous physiological and pathological contexts, our data indicate a novel common function for the Tenascin family in the regulation of tissue homeostasis under healthy and pathological conditions.
format Online
Article
Text
id pubmed-8155481
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-81554812021-05-28 Latent TGF-β Activation Is a Hallmark of the Tenascin Family Aubert, Alexandre Mercier-Gouy, Perrine Aguero, Stéphanie Berthier, Laurent Liot, Sophie Prigent, Laura Alcaraz, Lindsay B. Verrier, Bernard Terreux, Raphaël Moali, Catherine Lambert, Elise Valcourt, Ulrich Front Immunol Immunology Transforming growth factor-β (TGF-β) isoforms are secreted as inactive complexes formed through non-covalent interactions between bioactive TGF-β entities and their N-terminal pro-domains called latency-associated peptides (LAP). Extracellular activation of latent TGF-β within this complex is a crucial step in the regulation of TGF-β activity for tissue homeostasis and immune cell function. We previously showed that the matrix glycoprotein Tenascin-X (TN-X) interacted with the small latent TGF-β complex and triggered the activation of the latent cytokine into a bioactive TGF-β. This activation most likely occurs through a conformational change within the latent TGF-β complex and requires the C-terminal fibrinogen-like (FBG) domain of the glycoprotein. As the FBG-like domain is highly conserved among the Tenascin family members, we hypothesized that Tenascin-C (TN-C), Tenascin-R (TN-R) and Tenascin-W (TN-W) might share with TN-X the ability to regulate TGF-β bioavailability through their C-terminal domain. Here, we demonstrate that purified recombinant full-length Tenascins associate with the small latent TGF-β complex through their FBG-like domains. This association promotes activation of the latent cytokine and subsequent TGF-β cell responses in mammary epithelial cells, such as cytostasis and epithelial-to-mesenchymal transition (EMT). Considering the pleiotropic role of TGF-β in numerous physiological and pathological contexts, our data indicate a novel common function for the Tenascin family in the regulation of tissue homeostasis under healthy and pathological conditions. Frontiers Media S.A. 2021-05-13 /pmc/articles/PMC8155481/ /pubmed/34054795 http://dx.doi.org/10.3389/fimmu.2021.613438 Text en Copyright © 2021 Aubert, Mercier-Gouy, Aguero, Berthier, Liot, Prigent, Alcaraz, Verrier, Terreux, Moali, Lambert and Valcourt https://creativecommons.org/licenses/by/4.0/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.
spellingShingle Immunology
Aubert, Alexandre
Mercier-Gouy, Perrine
Aguero, Stéphanie
Berthier, Laurent
Liot, Sophie
Prigent, Laura
Alcaraz, Lindsay B.
Verrier, Bernard
Terreux, Raphaël
Moali, Catherine
Lambert, Elise
Valcourt, Ulrich
Latent TGF-β Activation Is a Hallmark of the Tenascin Family
title Latent TGF-β Activation Is a Hallmark of the Tenascin Family
title_full Latent TGF-β Activation Is a Hallmark of the Tenascin Family
title_fullStr Latent TGF-β Activation Is a Hallmark of the Tenascin Family
title_full_unstemmed Latent TGF-β Activation Is a Hallmark of the Tenascin Family
title_short Latent TGF-β Activation Is a Hallmark of the Tenascin Family
title_sort latent tgf-β activation is a hallmark of the tenascin family
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155481/
https://www.ncbi.nlm.nih.gov/pubmed/34054795
http://dx.doi.org/10.3389/fimmu.2021.613438
work_keys_str_mv AT aubertalexandre latenttgfbactivationisahallmarkofthetenascinfamily
AT merciergouyperrine latenttgfbactivationisahallmarkofthetenascinfamily
AT aguerostephanie latenttgfbactivationisahallmarkofthetenascinfamily
AT berthierlaurent latenttgfbactivationisahallmarkofthetenascinfamily
AT liotsophie latenttgfbactivationisahallmarkofthetenascinfamily
AT prigentlaura latenttgfbactivationisahallmarkofthetenascinfamily
AT alcarazlindsayb latenttgfbactivationisahallmarkofthetenascinfamily
AT verrierbernard latenttgfbactivationisahallmarkofthetenascinfamily
AT terreuxraphael latenttgfbactivationisahallmarkofthetenascinfamily
AT moalicatherine latenttgfbactivationisahallmarkofthetenascinfamily
AT lambertelise latenttgfbactivationisahallmarkofthetenascinfamily
AT valcourtulrich latenttgfbactivationisahallmarkofthetenascinfamily