FACIT collagens XII and XIV and their role in musculoskeletal homeostasis and regeneration

FACIT 胶原蛋白 XII 和 XIV 及其在肌肉骨骼稳态和再生中的作用

• 批准号: 407164344
• 负责人: Professor Dr. Manuel Koch
• 金额: --
• 依托单位: Cluster of Excellence: Cellular Stress Responses in Aging-Associated Diseases
• 依托单位国家: 德国
• 项目类别: Research Units
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/407164344?language=en
• 关键词: FACIT; collagens; XII; XIV; their

Proteins of the collagen family fulfil important functions for the musculoskeletal system. This is illustrated by collagen-dependent inherited diseases such as myopathy and Ehler-Danlos syndrome. A subgroup of collagens is attributed to collagen-associated proteins, and a protein within this group, termed collagen XII, was described for the first time in our laboratory as a protein secreted by skin fibroblasts. Recently, we were able to demonstrate its involvement in the extracellular matrix by describing new binding partners for collagen XII. With others, we were able to detect collagen XII mutations in several patient families, with these patients exhibiting myopathies, joint hypermobility and soft skin with atrophic scarring. Furthermore, we could detect changes in the knee in mice as well as in the patients, which can lead to patellar luxation. The aim of this project is to clarify the function of collagens XII and XIV in the neuromuscular system. In particular, we will investigate the role of collagens XII and XIV in muscle and nerve regeneration after injury. The molecular signalling pathways will also be investigated in more detail. In addition to understanding the function of collagens XII and XIV, this work will also serve to identify new therapeutic options for treatment

胶原蛋白家族的蛋白质对肌肉骨骼系统具有重要的功能。肌病和埃勒-当洛斯综合征等胶原依赖性遗传病就说明了这一点。胶原蛋白的一个亚组属于胶原蛋白相关蛋白，该组中的一种蛋白质称为胶原蛋白 XII，在我们的实验室中首次被描述为由皮肤成纤维细胞分泌的蛋白质。最近，我们通过描述 XII 型胶原蛋白的新结合伙伴，证明了它参与细胞外基质。与其他患者一起，我们能够在几个患者家族中检测到胶原蛋白 XII 突变，这些患者表现出肌病、关节过度活动和皮肤柔软并伴有萎缩性疤痕。此外，我们可以检测小鼠和患者膝盖的变化，这些变化可能导致髌骨脱位。该项目的目的是阐明胶原蛋白 XII 和 XIV 在神经肌肉系统中的功能。特别是，我们将研究胶原蛋白 XII 和 XIV 在损伤后肌肉和神经再生中的作用。分子信号传导途径也将得到更详细的研究。除了了解胶原蛋白 XII 和 XIV 的功能外，这项工作还将有助于确定新的治疗选择