骨骼肌失神经支配后骨骼肌干细胞在体内分化方向的研究

Fibrous tissue connected the gap of muscle fibres and repaired the injured skeletal muscle. There were a large number of active myofibroblasts. Muscle stem cells ,which mainly consists of muscle satellite cells(SCs) and muscle-derived stem cells (MDSCs), have multi-differentiation potential, forming either myoblasts or fibroblasts. It was not clear which kind of cells was activated and differentiates into myofibroblasts in the denervated skeletal muscle. We found out that in vitro MDSCs were induced to differentiate into myofibroblasts by TGF-ß1, and the TGF-β1/smads signal pathway takes part in the process of fibroblastic differentiation of skeletal (MDSCs) as well as the fibrosis of skeletal muscles under denervation. Therefore, we assumed that in vivo MDSCs differentiate into myofibroblasts which results in the fibrosis of the denervated skeletal muscle. This project intend to clarify the direction of the differentiation of SCs and MDSCs and its connection with fibrosis in vivo after periphery nerve injury. It will provide a new direction for preventing the fibrosis of the denervated skeletal muscle.

骨骼肌损伤后修复主要依赖肌肉间的纤维组织连接，其内有大量活化的myofibroblasts。肌肉干细胞主要包括肌卫星细胞（SCs）和肌源性干细胞（MDSCs），有多向分化能力，能成肌分化，也能成纤维样分化。骨骼肌失神经支配后，肌组织中哪类细胞活化为myofibroblasts促进肌萎缩纤维化还不清楚。申请人在国家自然科学基金的研究中发现：在体外，MDSCs 在TGF-ß1刺激下分化为myofibroblasts，TGF-ß1/Smads信号通路参与骨骼肌MDSCs的成纤维样分化和失神经骨骼肌纤维化过程。因此，我们假设：骨骼肌失神经支配后，MDSCs是最主要转分化为myofibroblasts，导致骨骼肌纤维化的细胞。本研究将明确周围神经损伤后，体内SCs和MDSCs的分化方向及其与肌肉纤维化的关系，为延缓骨骼肌失神经纤维化提供一个新的方向。