Serrano Antonio L, Muñoz-Cánoves Pura
Cell Biology Group, Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), CIBER on Neurodegenerative diseases (CIBERNED), Barcelona, Spain.
Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
Methods Mol Biol. 2021;2299:357-370. doi: 10.1007/978-1-0716-1382-5_24.
Fibrosis in skeletal muscle is the natural tissue response to persistent damage and chronic inflammatory states, cursing with altered muscle stem cell regenerative functions and increased activation of fibrogenic mesenchymal stromal cells. Exacerbated deposition of extracellular matrix components is a characteristic feature of human muscular dystrophies, neurodegenerative diseases affecting muscle and aging. The presence of fibrotic tissue not only impedes normal muscle contractile functions but also hampers effective gene and cell therapies. There is a lack of appropriate experimental models to study fibrosis. In this chapter, we highlight recent developments on skeletal muscle fibrosis in mice and expand previously described methods by our group to exacerbate and accelerate fibrosis development in murine muscular dystrophy models and to study the presence of fibrosis in muscle samples. These methods will help understand the molecular and biological mechanisms involved in muscle fibrosis and to identify novel therapeutic strategies to limit the progression of fibrosis in muscular dystrophy.
骨骼肌纤维化是机体对持续性损伤和慢性炎症状态的自然组织反应,伴有肌肉干细胞再生功能改变和促纤维化间充质基质细胞激活增加。细胞外基质成分的过度沉积是人类肌肉营养不良、影响肌肉的神经退行性疾病以及衰老的特征性表现。纤维化组织的存在不仅会阻碍正常肌肉收缩功能,还会妨碍有效的基因和细胞治疗。目前缺乏研究纤维化的合适实验模型。在本章中,我们重点介绍了小鼠骨骼肌纤维化的最新进展,并扩展了我们小组之前描述的方法,以加剧和加速小鼠肌肉营养不良模型中的纤维化发展,并研究肌肉样本中纤维化的存在情况。这些方法将有助于理解肌肉纤维化所涉及的分子和生物学机制,并确定限制肌肉营养不良中纤维化进展的新治疗策略。