Tenascin-C in fibrosis in multiple organs: Translational implications.
Tenascin-C in fibrosis in multiple organs: Translational implications.
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DOI：
10.1016/j.semcdb.2022.03.019
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发表时间：
2022-08
影响因子：
7.3
通讯作者：
Varga, John
中科院分区：
文献类型：
--
作者：
Bhattacharyya, Swati;Midwood, Kim S.;Varga, John
系统性硬化症（SSc，硬皮病）是一种复杂的疾病，具有自身免疫、血管病变和纤维化三重致病性，累及皮肤和多个内脏器官。由于纤维化占全世界所有死亡人数的45%，并且患病率似乎正在增加，因此了解其发病机制和进展是一项紧迫的科学挑战。成纤维细胞和肌成纤维细胞一方面是执行生理性组织修复的关键效应细胞，另一方面是导致慢性纤维化的病理性纤维形成。最近的研究发现，通过toll样受体（TLRs）的先天免疫信号是SSc持续纤维化反应的关键驱动因素。重复损伤触发原位产生“损伤相关分子模式”（DAMPs）或危险信号。TLR4对驻留细胞的这些危险信号的感知，引发了对纤维化基因表达和肌成纤维细胞分化的强烈刺激作用，引发了SSc自我维持的病理性纤维化特征的自我限制的组织修复反应。我们对与SSc相关的DAMPs进行了无偏调查，发现细胞外基质糖蛋白tenascin-C是SSc皮肤和肺活检中最高度上调的ECM蛋白之一。此外，tenascin C负责驱动持续的成纤维细胞激活，从而纤维化的进展。本文综述了近年来研究tenascin C的调控和复杂功能作用的研究，提出了tenascin- tlr4轴在病理性纤维化中的作用，以及针对其信号传导的新型抗纤维化方法。
Systemic sclerosis (SSc, scleroderma) is a complex disease with a pathogenic triad of autoimmunity, vasculopathy, and fibrosis involving the skin and multiple internal organs.Because fibrosis accounts for as much as 45% of all deaths worldwide and appears to be increasing in prevalence, understanding its pathogenesis and progression is an urgent scientific challenge. Fibroblasts and myofibroblasts are the key effector cells executing physiologic tissue repair on one hand, and pathological fibrogenesis leading to chronic fibrosing conditions on the other. Recent studies identify innate immune signaling via toll-like receptors (TLRs) as a key driver of persistent fibrotic response in SSc. Repeated injury triggers the in-situ generation of “damage-associated molecular patterns” (DAMPs) or danger signals. Sensing of these danger signals by TLR4 on resident cells elicits potent stimulatory effects on fibrotic gene expression and myofibroblast differentiation triggering the self-limited tissue repair response to self-sustained pathological fibrosis characteristic of SSc. Our unbiased survey for DAMPs associated with SSc identified extracellular matrix glycoprotein tenascin-C as one of the most highly up-regulated ECM proteins in SSc skin and lung biopsies. Furthermore, tenascin C is responsible for driving sustained fibroblasts activation, thereby progression of fibrosis. This review summarizes recent studies examining the regulation and complex functional role of tenascin C, presenting tenascin-TLR4 axis in pathological fibrosis, and novel anti-fibrotic approaches targeting their signaling.
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影响因子：
3.2
作者：
Chiovaro F;Chiquet-Ehrismann R;Chiquet M
通讯作者：
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影响因子：
8.2
作者：
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影响因子：
7.7
作者：
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通讯作者：
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影响因子：
3.1
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Molina-Molina M
影响因子：
7.3
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
通讯作者：
Valcourt U