Latent TGF-β Activation Is a Hallmark of the Tenascin Family.
Latent TGF-β Activation Is a Hallmark of the Tenascin Family.
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DOI：
10.3389/fimmu.2021.613438
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发表时间：
2021
影响因子：
7.3
通讯作者：
Valcourt U
中科院分区：
文献类型：
--
作者：
Aubert A;Mercier-Gouy P;Aguero S;Berthier L;Liot S;Prigent L;Alcaraz LB;Verrier B;Terreux R;Moali C;Lambert E;Valcourt U
转化生长因子-β (TGF-β)异构体是通过生物活性TGF-β实体与其n端前结构域（称为潜伏期相关肽（LAP））之间的非共价相互作用形成的非活性复合物分泌的。细胞外激活该复合体内潜伏的TGF-β是TGF-β活性调控组织稳态和免疫细胞功能的关键步骤。我们之前的研究表明，基质糖蛋白Tenascin-X （TN-X）与小的潜伏TGF-β复合物相互作用，并触发潜伏细胞因子的激活，形成具有生物活性的TGF-β。这种激活很可能是通过潜伏的TGF-β复合物的构象变化发生的，并且需要糖蛋白的c端纤维蛋白原样（FBG）结构域。由于fmg -like结构域在Tenascin家族成员中高度保守，我们假设Tenascin- c （TN-C）、Tenascin- r （TN-R）和Tenascin- w （TN-W）可能与TN-X共享通过其c端结构域调节TGF-β生物利用度的能力。在这里，我们证明纯化的重组全长Tenascins通过其fbg样结构域与小的潜伏TGF-β复合物结合。这种关联促进了乳腺上皮细胞中潜在细胞因子的激活和随后的TGF-β细胞反应，如细胞停滞和上皮-间质转化（EMT）。考虑到TGF-β在许多生理和病理环境中的多效性作用，我们的数据表明，在健康和病理条件下，Tenascin家族在调节组织稳态方面具有一种新的共同功能。
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.
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DOI：
10.1083/jcb.201308031
发表时间：
2014-05-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Alcaraz LB;Exposito JY;Chuvin N;Pommier RM;Cluzel C;Martel S;Sentis S;Bartholin L;Lethias C;Valcourt U
通讯作者：
Valcourt U
影响因子：
--
作者：
Brellier, Florence;Martina, Enrico;Chiquet-Ehrismann, Ruth
通讯作者：
Chiquet-Ehrismann, Ruth
影响因子：
7.2
作者：
Chiquet-Ehrismann, Ruth;Tucker, Richard P.
通讯作者：
Tucker, Richard P.
DOI：
10.1016/j.biocel.2003.12.002
发表时间：
2004-06-01
影响因子：
4
作者：
Chiquet-Ehrismann, R
通讯作者：
Chiquet-Ehrismann, R
胚胎鸡组织和人类肿瘤中的六边形蛋白。
影响因子：
7.8
作者：
Erickson, H P;Taylor, H C
通讯作者：
Taylor, H C