Jürgensen Henrik J, van Putten Sander, Nørregaard Kirstine S, Bugge Thomas H, Engelholm Lars H, Behrendt Niels, Madsen Daniel H
Finsen Laboratory, Rigshospitalet/Biotech Research and Innovation Center, University of Copenhagen, Ole Maaloesvej 5, 2200, Copenhagen N, Denmark.
Proteases and Tissue Remodeling Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, 20892, USA.
Cell Mol Life Sci. 2020 Aug;77(16):3161-3176. doi: 10.1007/s00018-020-03481-3. Epub 2020 Feb 25.
As the dominant constituent of the extracellular matrix (ECM), collagens of different types are critical for the structural properties of tissues and make up scaffolds for cellular adhesion and migration. Importantly, collagens also directly modulate the phenotypic state of cells by transmitting signals that influence proliferation, differentiation, polarization, survival, and more, to cells of mesenchymal, epithelial, or endothelial origin. Recently, the potential of collagens to provide immune regulatory signals has also been demonstrated, and it is believed that pathological changes in the ECM shape immune cell phenotype. Collagens are themselves heavily regulated by a multitude of structural modulations or by catabolic pathways. One of these pathways involves a cellular uptake of collagens or soluble collagen-like defense collagens of the innate immune system mediated by endocytic collagen receptors. This cellular uptake is followed by the degradation of collagens in lysosomes. The potential of this pathway to regulate collagens in pathological conditions is evident from the increased extracellular accumulation of both collagens and collagen-like defense collagens following endocytic collagen receptor ablation. Here, we review how endocytic collagen receptors regulate collagen turnover during physiological conditions and in pathological conditions, such as fibrosis and cancer. Furthermore, we highlight the potential of collagens to regulate immune cells and discuss how endocytic collagen receptors can directly regulate immune cell activity in pathological conditions or do it indirectly by altering the extracellular milieu. Finally, we discuss the potential collagen receptors utilized by immune cells to directly detect ECM-related changes in the tissues which they encounter.
作为细胞外基质（ECM）的主要成分，不同类型的胶原蛋白对于组织的结构特性至关重要，并构成细胞黏附和迁移的支架。重要的是，胶原蛋白还通过向间充质、上皮或内皮来源的细胞传递影响增殖、分化、极化、存活等的信号，直接调节细胞的表型状态。最近，胶原蛋白提供免疫调节信号的潜力也得到了证实，并且人们认为细胞外基质的病理变化塑造了免疫细胞表型。胶原蛋白本身受到多种结构调节或分解代谢途径的严格调控。其中一条途径涉及由内吞性胶原蛋白受体介导的细胞对胶原蛋白或先天免疫系统中可溶性胶原样防御胶原蛋白的摄取。这种细胞摄取之后是溶酶体中胶原蛋白的降解。内吞性胶原蛋白受体消融后，胶原蛋白和胶原样防御胶原蛋白在细胞外的积累增加，这表明该途径在病理条件下调节胶原蛋白的潜力。在这里，我们综述了内吞性胶原蛋白受体在生理条件下以及在诸如纤维化和癌症等病理条件下如何调节胶原蛋白的周转。此外，我们强调了胶原蛋白调节免疫细胞的潜力，并讨论了内吞性胶原蛋白受体如何在病理条件下直接调节免疫细胞活性或通过改变细胞外环境间接调节免疫细胞活性。最后，我们讨论了免疫细胞用于直接检测它们所遇到的组织中与细胞外基质相关变化的潜在胶原蛋白受体。
