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Implication des membres de la famille des Ténascines dans la régulation de la biodisponibilité du TGF-β latent

Abstract : Tenascin is a family of complex glycoproteins of the extracellular matrix composed offour members: Tenascin-C (TN-C), Tenascin-R (TN-R), Tenascin-W (TN-W) andTenascin-X (TN-X). These proteins have very specific expression profiles in adultwhich are often deregulated during tumor progression. It has been shown that TN-X,in addition to its architectural function within the extracellular matrix, is also able toregulate cell signaling. Indeed, TN-X activates latent Transforming Growth Factor(TGF)-Beta, a cytokine secreted by cells in an inactive form, thanks to its C-terminaldomain resembling to the fibrinogen (FBG-like domain). This domain is highly conserved between Tenascin family members. Thus, we demonstrated that TN-C, TNR and TN-W are also able to activate latent TGF-Beta through their FBG-like domainsin vitro. Such activation presents mature TGF-Beta to cell surface, leading to the activation of a functional TGF-Beta/Smad intracellular pathway. We also found thatFBG-like domain of Tenascins induce cytostasis and trigger epithelial-tomesenchymaltransition in epithelial cells, two responses induced by bioactive TGFBeta. Finally, we started a side project aiming at the characterization of FBG-Xvariations found in patients suffering from classical-like Ehlers-Danlos syndrome. This study investigates the impact of these variations on TN-X ability to activate latent TGF-Beta.
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Submitted on : Tuesday, February 23, 2021 - 11:32:35 AM
Last modification on : Wednesday, March 10, 2021 - 11:31:23 AM


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  • HAL Id : tel-03135810, version 2



Alexandre Aubert. Implication des membres de la famille des Ténascines dans la régulation de la biodisponibilité du TGF-β latent. Biochimie, Biologie Moléculaire. Université de Lyon, 2020. Français. ⟨NNT : 2020LYSEN088⟩. ⟨tel-03135810v2⟩



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