Muscle strains are a common injury that can occur during physical activity or exercise, and they can range from mild to severe depending on the extent of the damage. The mTOR pathway is a highly conserved signaling pa...Muscle strains are a common injury that can occur during physical activity or exercise, and they can range from mild to severe depending on the extent of the damage. The mTOR pathway is a highly conserved signaling pathway that has been implicated in various cellular processes, including tissue regeneration. Previous studies that have investigated protein synthesis in mice have concluded that the mTOR pathway can improve muscle regeneration. However, the specific effects of mTOR pathway activation on muscle regeneration in planarians have yet to be fully explored. Therefore, this study aimed to investigate the use of Arginine and Leucine to stimulate the mTOR pathway for muscle strains in planarians. During the experiment, planarians were amputated, and different dosages of Arginine and Leucine were used to stimulate the mTOR pathway in Dugesia dorotocephala. The speed of muscle regeneration was measured over 14 days in five groups, with thirty planarians in each group. The results showed that the rate of regeneration from 0.134 mM Leucine solution showed a significant increase compared to the control group, while the groups exposed to 0.1, 0.3 mM Arginine, and 0.0134 Leucine did not show significant changes in muscle regeneration. These findings suggest that mTOR pathway activation may enhance muscle regeneration in planarians and that the effects may be dose-dependent. These findings have important implications for developing new treatments for tissue damage. Further studies are needed to fully understand the mechanisms of mTOR pathway activation on muscle regeneration in planarians and its potential use in tissue engineering and regenerative medicine.展开更多
AIM: To study regeneration of damaged human and murine muscle implants and the contribution of added xenogeneic mesenchymal stem cells(MSCs).METHODS: Minced human or mouse skeletal muscle tissues were implanted togeth...AIM: To study regeneration of damaged human and murine muscle implants and the contribution of added xenogeneic mesenchymal stem cells(MSCs).METHODS: Minced human or mouse skeletal muscle tissues were implanted together with human or mouse MSCs subcutaneously on the back of non-obese diabetic/severe combined immunodeficient mice. The muscle tissues(both human and murine) were minced with scalpels into small pieces(< 1 mm3) and aliquoted in portions of 200 mm3. These portions were either cryopreserved in 10% dimethylsulfoxide or freshly implanted. Syngeneic or xenogeneic MSCs were added to the minced muscles directly before implantation. Implants were collected at 7, 14, 30 or 45 d after transplantation and processed for(immuno)histological analysis. The progression of muscle regeneration was assessed using a standard histological staining(hematoxylin-phloxinsaffron). Antibodies recognizing Pax7 and von Willebrand factor were used to detect the presence of satellite cells and blood vessels, respectively. To enable detection of the bone marrow-derived MSCs or their derivatives we used MSCs previously transduced with lentiviral vectors expressing a cytoplasmic LacZ gene. X-gal staining of the fixed tissues was used to detect β-galactosidase-positive cells and myofibers.RESULTS: Myoregeneration in implants of fresh murine muscle was evident as early as day 7, and progressed with time to occupy 50% to 70% of the implants. Regeneration of fresh human muscle was slower. These observations of fresh muscle implants were in contrast to the regeneration of cryopreserved murine muscle that proceeded similarly to that of fresh tissue except for day 45(P < 0.05). Cryopreserved human muscle showed minimal regeneration, suggesting that the freezing procedure was detrimental to human satellite cells. In fresh and cryopreserved mouse muscle supplemented with LacZ-tagged mouse MSCs, β-galactosidase-positive myofibers were identified early after grafting at the wellvascularized periphery of the implants. The contribution of human 展开更多
RING finger protein 13 （RNF13） is a newly identified E3 ligase reported to be functionally significant in the reg- ulation of cancer development, muscle cell growth, and neuronal development. In this study, the func...RING finger protein 13 （RNF13） is a newly identified E3 ligase reported to be functionally significant in the reg- ulation of cancer development, muscle cell growth, and neuronal development. In this study, the function of RNF13 in cardiotoxin-induced skeletal muscle regener- ation was investigated using RNF13-knockout mice. RNF13-/- mice exhibited enhanced muscle regeneration --characterized by accelerated satellite cell proliferation --compared with wild-type mice. The expression of RNF13 was remarkably induced in macrophages rather than in the satellite cells of wild-type mice at the very early stage of muscle damage. This result indicated that inflammatory cells are important in RNF13-mediated satellite cell functions. The cytokine levels in skeletal muscles were further analyzed and showed that RNF13＂i＂ mice produced greater amounts of various cytokines than wild-type mice. Among these, IL-4 and IL-6 levels significantly increased in RNF13-/＂ mice. The accelerated muscle regeneration phenotype was abrogated by inhibiting IL-4/IL-6 action in RNF13＂/- mice with blocking antibodies. These results indicate that RNF13 deficiency promotes skeletal muscle regeneration via the effects on satellite cell niche mediated by IL-4 and IL-6.展开更多
骨骼肌衰减症以及损伤或萎缩后肌肉再生修复的相关缺陷是人口老龄化结构中的一个主要公共健康问题,对行动能力、独立性和生活质量产生严重影响,并缺乏真正有效的预防与治疗策略。肌肉损伤后启动了一个高度协调的修复过程,存在一个由免...骨骼肌衰减症以及损伤或萎缩后肌肉再生修复的相关缺陷是人口老龄化结构中的一个主要公共健康问题,对行动能力、独立性和生活质量产生严重影响,并缺乏真正有效的预防与治疗策略。肌肉损伤后启动了一个高度协调的修复过程,存在一个由免疫、炎症细胞、细胞因子以及影响肌肉干细胞增殖和分化生长因子组成的复杂网络。调节性T细胞(regulatory T cells,Treg)在肌肉损伤修复与再生过程发挥不可或缺的作用,Treg细胞通过IL-33∶ST2蛋白轴的作用激活,并被大量招募至损伤部位,促进M1促炎症表型巨噬细胞向M2抗炎表型巨噬细胞转换并释放特殊生长因子双调节素Areg,刺激肌卫星细胞分化和肌肉再生。这些研究证据支持Treg细胞作为慢性肌肉疾病、肌肉衰减症等肌肉损伤或萎缩疾病的潜在治疗靶点,并证明了免疫机制在骨骼肌组织修复中具有核心的稳态作用,为慢性肌肉疾病和衰老肌肉的再生医学研究和治疗开辟了新的前景。展开更多
文摘Muscle strains are a common injury that can occur during physical activity or exercise, and they can range from mild to severe depending on the extent of the damage. The mTOR pathway is a highly conserved signaling pathway that has been implicated in various cellular processes, including tissue regeneration. Previous studies that have investigated protein synthesis in mice have concluded that the mTOR pathway can improve muscle regeneration. However, the specific effects of mTOR pathway activation on muscle regeneration in planarians have yet to be fully explored. Therefore, this study aimed to investigate the use of Arginine and Leucine to stimulate the mTOR pathway for muscle strains in planarians. During the experiment, planarians were amputated, and different dosages of Arginine and Leucine were used to stimulate the mTOR pathway in Dugesia dorotocephala. The speed of muscle regeneration was measured over 14 days in five groups, with thirty planarians in each group. The results showed that the rate of regeneration from 0.134 mM Leucine solution showed a significant increase compared to the control group, while the groups exposed to 0.1, 0.3 mM Arginine, and 0.0134 Leucine did not show significant changes in muscle regeneration. These findings suggest that mTOR pathway activation may enhance muscle regeneration in planarians and that the effects may be dose-dependent. These findings have important implications for developing new treatments for tissue damage. Further studies are needed to fully understand the mechanisms of mTOR pathway activation on muscle regeneration in planarians and its potential use in tissue engineering and regenerative medicine.
基金Supported by A scholarship to AS de la Garza-Rodea from the Universidad Autonoma de Nuevo Leon,Monterrey,Mexico
文摘AIM: To study regeneration of damaged human and murine muscle implants and the contribution of added xenogeneic mesenchymal stem cells(MSCs).METHODS: Minced human or mouse skeletal muscle tissues were implanted together with human or mouse MSCs subcutaneously on the back of non-obese diabetic/severe combined immunodeficient mice. The muscle tissues(both human and murine) were minced with scalpels into small pieces(< 1 mm3) and aliquoted in portions of 200 mm3. These portions were either cryopreserved in 10% dimethylsulfoxide or freshly implanted. Syngeneic or xenogeneic MSCs were added to the minced muscles directly before implantation. Implants were collected at 7, 14, 30 or 45 d after transplantation and processed for(immuno)histological analysis. The progression of muscle regeneration was assessed using a standard histological staining(hematoxylin-phloxinsaffron). Antibodies recognizing Pax7 and von Willebrand factor were used to detect the presence of satellite cells and blood vessels, respectively. To enable detection of the bone marrow-derived MSCs or their derivatives we used MSCs previously transduced with lentiviral vectors expressing a cytoplasmic LacZ gene. X-gal staining of the fixed tissues was used to detect β-galactosidase-positive cells and myofibers.RESULTS: Myoregeneration in implants of fresh murine muscle was evident as early as day 7, and progressed with time to occupy 50% to 70% of the implants. Regeneration of fresh human muscle was slower. These observations of fresh muscle implants were in contrast to the regeneration of cryopreserved murine muscle that proceeded similarly to that of fresh tissue except for day 45(P < 0.05). Cryopreserved human muscle showed minimal regeneration, suggesting that the freezing procedure was detrimental to human satellite cells. In fresh and cryopreserved mouse muscle supplemented with LacZ-tagged mouse MSCs, β-galactosidase-positive myofibers were identified early after grafting at the wellvascularized periphery of the implants. The contribution of human
文摘RING finger protein 13 （RNF13） is a newly identified E3 ligase reported to be functionally significant in the reg- ulation of cancer development, muscle cell growth, and neuronal development. In this study, the function of RNF13 in cardiotoxin-induced skeletal muscle regener- ation was investigated using RNF13-knockout mice. RNF13-/- mice exhibited enhanced muscle regeneration --characterized by accelerated satellite cell proliferation --compared with wild-type mice. The expression of RNF13 was remarkably induced in macrophages rather than in the satellite cells of wild-type mice at the very early stage of muscle damage. This result indicated that inflammatory cells are important in RNF13-mediated satellite cell functions. The cytokine levels in skeletal muscles were further analyzed and showed that RNF13＂i＂ mice produced greater amounts of various cytokines than wild-type mice. Among these, IL-4 and IL-6 levels significantly increased in RNF13-/＂ mice. The accelerated muscle regeneration phenotype was abrogated by inhibiting IL-4/IL-6 action in RNF13＂/- mice with blocking antibodies. These results indicate that RNF13 deficiency promotes skeletal muscle regeneration via the effects on satellite cell niche mediated by IL-4 and IL-6.
文摘骨骼肌衰减症以及损伤或萎缩后肌肉再生修复的相关缺陷是人口老龄化结构中的一个主要公共健康问题,对行动能力、独立性和生活质量产生严重影响,并缺乏真正有效的预防与治疗策略。肌肉损伤后启动了一个高度协调的修复过程,存在一个由免疫、炎症细胞、细胞因子以及影响肌肉干细胞增殖和分化生长因子组成的复杂网络。调节性T细胞(regulatory T cells,Treg)在肌肉损伤修复与再生过程发挥不可或缺的作用,Treg细胞通过IL-33∶ST2蛋白轴的作用激活,并被大量招募至损伤部位,促进M1促炎症表型巨噬细胞向M2抗炎表型巨噬细胞转换并释放特殊生长因子双调节素Areg,刺激肌卫星细胞分化和肌肉再生。这些研究证据支持Treg细胞作为慢性肌肉疾病、肌肉衰减症等肌肉损伤或萎缩疾病的潜在治疗靶点,并证明了免疫机制在骨骼肌组织修复中具有核心的稳态作用,为慢性肌肉疾病和衰老肌肉的再生医学研究和治疗开辟了新的前景。
