Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
J Histochem Cytochem. 2018 Apr;66(4):289-304. doi: 10.1369/0022155418757443. Epub 2018 Jan 31.
To protect against danger, the innate immune system must promptly and accurately sense alarm signals, and mount an appropriate response to restore homeostasis. One endogenous trigger of immunity is tenascin-C, a large hexameric protein of the extracellular matrix. Upregulated upon tissue injury and cellular stress, tenascin-C is expressed during inflammation and tissue remodeling, where it influences cellular behavior by interacting with a multitude of molecular targets, including other matrix components, cell surface proteins, and growth factors. Here, we discuss how these interactions confer upon tenascin-C distinct immunomodulatory capabilities that make this matrix molecule necessary for efficient tissue repair. We also highlight in vivo studies that provide insight into the consequences of misregulated tenascin-C expression on inflammation and fibrosis during a wide range of inflammatory diseases. Finally, we examine how its unique expression pattern and inflammatory actions make tenascin-C a viable target for clinical exploitation in both diagnostic and therapeutic arenas.
为了防范危险，先天免疫系统必须迅速而准确地感知警报信号，并做出适当的反应以恢复体内平衡。一种内源性的免疫触发物是 tenascin-C，一种细胞外基质的大型六聚体蛋白。在组织损伤和细胞应激时上调，tenascin-C 在炎症和组织重塑期间表达，通过与多种分子靶标相互作用（包括其他基质成分、细胞表面蛋白和生长因子）影响细胞行为。在这里，我们讨论了这些相互作用如何赋予 tenascin-C 独特的免疫调节能力，使这种基质分子成为有效组织修复所必需的。我们还强调了体内研究，这些研究深入了解了在广泛的炎症性疾病中，tenascin-C 表达失调对炎症和纤维化的影响。最后，我们研究了其独特的表达模式和炎症作用如何使 tenascin-C 成为在诊断和治疗领域中具有临床应用潜力的可行靶标。
