The thymus regulates skeletal muscle regeneration by directly promoting satellite cell expansion
| Autor: | Yan-Yan Zheng, Ye Wang, Xin Chen, Li-Sha Wei, Han Wang, Tao Tao, Yu-Wei Zhou, Zhi-Hui Jiang, Tian-Tian Qiu, Zhi-Yuan Sun, Jie Sun, Pei Wang, Wei Zhao, Ye-Qiong Li, Hua-Qun Chen, Min-Sheng Zhu, Xue-Na Zhang |
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| Rok vydání: | 2022 |
| Předmět: |
SCM
splenocyte-conditioned medium Satellite Cells Skeletal Muscle proliferation Thymus Gland BrdU 5-Bromo-2′-deoxyuridine Muscle Development Biochemistry Mice FBS fetal bovine serum thymus FACS fluorescence-activated cell sorting skeletal muscle regeneration Animals Regeneration EdU 5-ethynyl-29-deoxyuridine Muscle Skeletal eMHC embryonic/developmental myosin heavy chain MyoG myogenin Molecular Biology Cell Proliferation MyoD Protein satellite cells Wound Healing TA tibialis anterior PAX7 Transcription Factor ConA concanavalin Cell Differentiation Cell Biology Pax7 paired box 7 conditioned medium TECs thymic epithelial cells TCM thymocyte-conditioned medium TCM-L lymphocytic TCM Research Article |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 0021-9258 |
| DOI: | 10.1016/j.jbc.2021.101516 |
| Popis: | The thymus is the central immune organ, but it is known to progressively degenerate with age. As thymus degeneration is paralleled by the wasting of aging skeletal muscle, we speculated that the thymus may play a role in muscle wasting. Here, using thymectomized mice, we show that the thymus is necessary for skeletal muscle regeneration, a process tightly associated with muscle aging. Compared to control mice, the thymectomized mice displayed comparable growth of muscle mass, but decreased muscle regeneration in response to injury, as evidenced by small and sparse regenerative myofibers along with inhibited expression of regeneration-associated genes myh3, myod, and myogenin. Using paired box 7 (Pax7)-immunofluorescence staining and 5-Bromo-2′-deoxyuridine-incorporation assay, we determined that the decreased regeneration capacity was caused by a limited satellite cell pool. Interestingly, the conditioned culture medium of isolated thymocytes had a potent capacity to directly stimulate satellite cell expansion in vitro. These expanded cells were enriched in subpopulations of quiescent satellite cells (Pax7highMyoDlowEdUpos) and activated satellite cells (Pax7highMyoDhighEdUpos), which were efficiently incorporated into the regenerative myofibers. We thus propose that the thymus plays an essential role in muscle regeneration by directly promoting satellite cell expansion and may function profoundly in the muscle aging process. |
| Databáze: | OpenAIRE |
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