Yuan Zhiyao, Smith Patricio, McCulloch Christopher A
Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, China.
Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
FASEB J. 2025 Jan 15;39(1):e70286. doi: 10.1096/fj.202402322R.
Periodontitis is an inflammatory disease triggered by microbial biofilms that promote immune dysfunction and tissue destruction of tooth-supporting tissues. The search for soluble mediators that amplify inflammatory responses and matrix degradation in periodontal tissues has implicated extracellular vimentin (ECV) as a signaling ligand and damage-associated molecular pattern in the pathogenesis of periodontitis. Intracellular vimentin filaments are essential for the structural integrity of cells and the preservation of matrix homeostasis. These are important determinants of health in the periodontium and many other organs. But in inflamed tissues, intracellular vimentin filaments are disassembled. Vimentin is subsequently released from cells into the extracellular space in a soluble form where it drives immune signaling and tissue destruction. We discuss the role of ECV as a signaling molecule in several tissues. We apply these data to understand how in inflammatory diseases like periodontitis, ECV amplifies immune responses that contribute to disease progression. Arising from these data, we consider novel therapeutic opportunities for limiting tissue destruction by targeting ECV for treatment of inflammatory disorders like periodontitis.
牙周炎是一种由微生物生物膜引发的炎症性疾病，会导致牙齿支持组织的免疫功能紊乱和组织破坏。寻找能够放大牙周组织炎症反应和基质降解的可溶性介质的研究表明，细胞外波形蛋白（ECV）在牙周炎发病机制中作为一种信号配体和损伤相关分子模式发挥作用。细胞内波形蛋白丝对于细胞的结构完整性和基质稳态的维持至关重要。这些是牙周组织和许多其他器官健康的重要决定因素。但在炎症组织中，细胞内波形蛋白丝会解体。波形蛋白随后以可溶形式从细胞释放到细胞外空间，在那里它驱动免疫信号传导和组织破坏。我们讨论了ECV作为信号分子在几种组织中的作用。我们应用这些数据来理解在牙周炎等炎症性疾病中，ECV如何放大促成疾病进展的免疫反应。基于这些数据，我们考虑通过靶向ECV来限制组织破坏，从而为治疗牙周炎等炎症性疾病带来新的治疗机会。
