The thymus regulates skeletal muscle regeneration by directly promoting satellite cell expansion

Zheng, Yanyan; Wang, Ye; Chen, Xin; Wei, Lisha; Wang, Han; Tao, Tao; Zhou, Yu-Wei; Jiang, Zhihui; Qiu, Tiantian; Sun, Zhiyuan; Sun, Jie; Wang, Pei; Zhao, Wei; Li, Ye-Qiong; Chen, Huaqun; Zhu, Min–Sheng; Zhang, Xuena

doi:10.1016/j.jbc.2021.101516

Cited by 6 publications

(4 citation statements)

References 70 publications

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“…The animal experiments were approved by the Experimental Committee of Nanjing Normal University (No: IACYUC-1903023; Approval date: 1 March 2019). The muscle injury model was established as described in our previous study [ 47 ]. Briefly, 30 µL of 1.2% BaCl 2 (Sigma-Aldrich) (St. Louis, MO, USA) dissolved in saline was injected into the tibialis anterior (TA) muscle.…”

Section: Methodsmentioning

confidence: 99%

Tetrandrine Inhibits Skeletal Muscle Differentiation by Blocking Autophagic Flux

Shi

Liu

et al. 2022

IJMS

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Tetrandrine is well known to act as a calcium channel blocker. It is a potential candidate for a tumor chemotherapy drug without toxicity. Tetrandrine inhibits cancer cell proliferation and induces cell death through apoptosis and autophagy. As cancer patients usually experience complications with sarcopenia or muscle injury, we thus assessed the effects of tetrandrine on skeletal muscle cells. We report in this study that a low dose of tetrandrine (less than 5 μM) does not affect the proliferation of C2C12 myoblasts, but significantly inhibits myogenic differentiation. Consistently, tetrandrine inhibited muscle regeneration after BaCl2-induced injury. Mechanistic experiments showed that tetrandrine decreased the p-mTOR level and increased the levels of LC3 and SQSTM1/p62 during differentiation. Ad-mRFP-GFP-LC3B transfection experiments revealed that the lysosomal quenching of GFP signals was suppressed by tetrandrine. Furthermore, the levels of DNM1L/Drp1, PPARGA1 and cytochrome C (Cyto C), as well as caspase 3 activation and ROS production, were decreased following tetrandrine administration, indicating that the mitochondrial network signaling was inhibited. Our results indicate that tetrandrine has dual effects on autophagic flux in myoblasts during differentiation, activation in the early stage and blockade in the late stage. The ultimate blocking of autophagic flux by tetrandrine led to the disruption of mitochondria remodeling and inhibition of myogenic differentiation. The inhibitory effects of tetrandrine on skeletal muscle differentiation may limit its application in advanced cancer patients. Thus, great attention should be paid to the clinical use of tetrandrine for cancer therapy.

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Section: Methodsmentioning

confidence: 99%

Tetrandrine Inhibits Skeletal Muscle Differentiation by Blocking Autophagic Flux

Shi

Liu

et al. 2022

IJMS

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“…The CD3 + CD4 + CD8 + thymocyte subset significantly induced proliferation in satellite cells, although CD4 + CD8 − and CD4 − CD8 + SP thymocytes also displayed a significant effect compared to the control. In contrast, Treg cells had no significant effect in a muscle injury model of thymectomized mice ( 125 ). In view of the above data, it seems that the thymus plays a role in the skeletal muscle by its influence on regeneration.…”

Section: Thymus Defects Underlying Peripheral T Cell Biology Abnormal...mentioning

confidence: 99%

“…Interestingly, the thymus may play a role in the skeletal muscle regeneration process. A study carried out in a model of induced skeletal muscle injury showed that the mean cross-sectional area of regenerating myofibers and the number of myofibers in 8–10 weeks of age thymectomized mice were impaired compared to euthymic controls ( 125 ). In addition to this defect in muscle regeneration, thymectomized mice also showed decreased levels of myoblast determination proteins, MyoD 1 and myogenin (MyoG), important myogenic factors for skeletal muscle regeneration.…”

Section: Thymus Defects Underlying Peripheral T Cell Biology Abnormal...mentioning

confidence: 99%

T cell biology in neuromuscular disorders: a focus on Duchenne Muscular Dystrophy and Amyotrophic Lateral Sclerosis

Lemos,

Tenório,

Mouly

et al. 2023

Front. Immunol.

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Growing evidence demonstrates a continuous interaction between the immune system, the nerve and the muscle in neuromuscular disorders of different pathogenetic origins, such as Duchenne Muscular Dystrophy (DMD) and Amyotrophic Lateral Sclerosis (ALS), the focus of this review. Herein we highlight the complexity of the cellular and molecular interactions involving the immune system in neuromuscular disorders, as exemplified by DMD and ALS. We describe the distinct types of cell-mediated interactions, such as cytokine/chemokine production as well as cell-matrix and cell-cell interactions between T lymphocytes and other immune cells, which target cells of the muscular or nervous tissues. Most of these interactions occur independently of exogenous pathogens, through ligand-receptor binding and subsequent signal transduction cascades, at distinct levels of specificity. Although this issue reveals the complexity of the system, it can also be envisioned as a window of opportunity to design therapeutic strategies (including synthetic moieties, cell and gene therapy, as well as immunotherapy) by acting upon one or more targets. In this respect, we discuss ongoing clinical trials using VLA-4 inhibition in DMD, and in ALS, with a focus on regulatory T cells, both revealing promising results.

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“…The thymus is considered as the central lymphoid organ for production of diverse immune cells and provides proper environments for T lymphocytes maturation, differentiation, and function [ 14 ]. The mature T cells in the thymus can migrate to the lymph nodes, aiding the immune system to fight the disease [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

L-Citrulline Supplementation Restrains Ferritinophagy-Mediated Ferroptosis to Alleviate Iron Overload-Induced Thymus Oxidative Damage and Immune Dysfunction

Zhao

Chen

et al. 2022

Nutrients

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L-citrulline (L-cit) is a key intermediate in the urea cycle and is known to possess antioxidant and anti-inflammation characteristics. However, the role of L-cit in ameliorating oxidative damage and immune dysfunction against iron overload in the thymus remains unclear. This study explored the underlying mechanism of the antioxidant and anti-inflammation qualities of L-cit on iron overload induced in the thymus. We reported that L-cit administration could robustly alleviate thymus histological damage and reduce iron deposition, as evidenced by the elevation of the CD8+ T lymphocyte number and antioxidative capacity. Moreover, the NF-κB pathway, NCOA4-mediated ferritinophagy, and ferroptosis were attenuated. We further demonstrated that L-cit supplementation significantly elevated the mTEC1 cells’ viability and reversed LDH activity, iron levels, and lipid peroxidation caused by FAC. Importantly, NCOA4 knockdown could reduce the intracellular cytoplasmic ROS, which probably relied on the Nfr2 activation. The results subsequently indicated that NCOA4-mediated ferritinophagy was required for ferroptosis by showing that NCOA4 knockdown reduced ferroptosis and lipid ROS, accompanied with mitochondrial membrane potential elevation. Intriguingly, L-cit treatment significantly inhibited the NF-κB pathway, which might depend on restraining ferritinophagy-mediated ferroptosis. Overall, this study indicated that L-cit might target ferritinophagy-mediated ferroptosis to exert antioxidant and anti-inflammation capacities, which could be a therapeutic strategy against iron overload-induced thymus oxidative damage and immune dysfunction.

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The thymus regulates skeletal muscle regeneration by directly promoting satellite cell expansion

Cited by 6 publications

References 70 publications

Tetrandrine Inhibits Skeletal Muscle Differentiation by Blocking Autophagic Flux

Tetrandrine Inhibits Skeletal Muscle Differentiation by Blocking Autophagic Flux

T cell biology in neuromuscular disorders: a focus on Duchenne Muscular Dystrophy and Amyotrophic Lateral Sclerosis

L-Citrulline Supplementation Restrains Ferritinophagy-Mediated Ferroptosis to Alleviate Iron Overload-Induced Thymus Oxidative Damage and Immune Dysfunction

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