徳島大学大学院医歯薬学研究部生体栄養学分野※Graduate School of Biomedical Sciences, Tokushima University※― 61 ―Skeletal muscle has remarkable regeneration potential, but under various pathological conditions, regeneration fails, resulting in muscle atrophy and loss of function. Muscle satellite cells, the stem cells of skeletal muscle, play a central role in regeneration by generating new myofibers. Alongside muscle satellite cells, macrophages (MΦs) are also important. Since it has been shown that loss of MΦs severely impairs regeneration, acute inflammation caused by MΦs is essential for muscle regeneration. On the other hand, inflammation must be resolved, which requires the conversion of MΦs from inflammatory to anti-inflammatory phenotype. Inflammatory MΦs promote muscle satellite cell proliferation, while anti-inflammatory MΦs promote muscle differentiation. This regulation of MΦs is important, as regeneration is impaired by persistent inflammation in muscle diseases and ageing. However, the regulatory mechanisms of MΦs remain unclear. We have identified mesenchymal stromal cells (MSCs) residing muscle interstitial space and demonstrated that they play a supportive role in muscle regeneration. On the other hand, MSCs have also been known to contribute to pathological degeneration, such as fat infiltration and fibrosis in muscle. In the course of analyzing the dual nature of MSCs (properties that support muscle regeneration and those that cause pathological degeneration), we found that cell-autonomous retinoic acid (RA) signaling in MSCs is required for the acquisition of muscle regeneration-supporting functions. Furthermore, functional analysis of RA signaling in MSCs showed that activation of RA signaling in MSCs is required for both efficient muscle repair and resolution of inflammation. This study reveals a novel function of MSCs that links two important biological events: tissue regeneration and inflammation resolution.※九州大学生体防御医学研究所細胞不均一性学分野※Division of Cell Heterogeneity, Medical Institute of Bioregulation, Kyushu UniversityAbstract組織再生と炎症の収束を連動させる筋・免疫連関Mechanisms…coupling…tissue…regenerationand…inflammation…resolution上住 聡芳Akiyoshi Uezumi
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