Interleukin-15 facilitates muscle regeneration through modulation of fibro/adipogenic progenitors.
Xia Kang,Yang Mingyu,Youxing Shi,Mei-ming Xie,Min Zhu,Xiaolong Zheng,Zhang Chenke,Zilu Ge,Bian Xuting,Jing-tong Lv,Yunjiao Wang,Binghua Zhou,Kanglai Tang +12 more
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The findings supported the potential role of IL-15 as a modulator on fate of FAPs in injured muscle and as a novel therapy for chronic muscle injury.Abstract:
Chronic muscle injury is characteristics of fatty infiltration and fibrosis. Recently, fibro/adipogenic progenitors (FAPs) were found to be indispensable for muscular regeneration while were also responsible for fibrosis and fatty infiltration in muscle injury. Many myokines have been proven to regulate the adipose or cell proliferation. Because the fate of FAPs is largely dependent on microenvironment and the regulation of myokines on FAPs is still unclear. We screened the potential myokines and found Interleukin-15 (IL-15) may regulate the fatty infiltration in muscle injury. In this study, we investigated how IL-15 regulated FAPs in muscle injury and the effect on muscle regeneration. Cell proliferation assay, western blots, qRT-PCR, immunohistochemistry, flow cytometric analysis were performed to investigate the effect of IL-15 on proliferation and adipogensis of FAPs. Acute muscle injury was induced by injection of glycerol or cardiotoxin to analyze how IL-15 effected on FAPs in vivo and its function on fatty infiltration or muscle regeneration. We identified that the expression of IL-15 in injured muscle was negatively associated with fatty infiltration. IL-15 can stimulate the proliferation of FAPs and prevent the adipogenesis of FAPs in vitro and in vivo. The growth of FAPs caused by IL-15 was mediated through JAK-STAT pathway. In addition, desert hedgehog pathway may participate in IL-15 inhibiting adipogenesis of FAPs. Our study showed IL-15 can cause the fibrosis after muscle damage and promote the myofiber regeneration. Finally, the expression of IL-15 was positively associated with severity of fibrosis and number of FAPs in patients with chronic rotator cuff tear. These findings supported the potential role of IL-15 as a modulator on fate of FAPs in injured muscle and as a novel therapy for chronic muscle injury.read more
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Skeletal muscle as potential central link between sarcopenia and immune senescence.
TL;DR: The current - however still fragmentary - knowledge about the potential communication pathways of muscle and immune system, how they are affected by aging of skeletal muscle and possible treatment strategies are outlined and should stimulate further research in this important scientific field.
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Fibro-Adipogenic Progenitors Cross-Talk in Skeletal Muscle: The Social Network.
TL;DR: This review will focus on the soluble factors that regulate FAPs activity, highlighting their roles in orchestrating the inter-cellular interactions between F APs and the other cell populations that participate in muscle regeneration.
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Biomaterial and stem cell‐based strategies for skeletal muscle regeneration
TL;DR: The stem cell populations that can stimulate muscle regeneration in vitro and in vivo are reviewed and the regenerative potential of combination therapies that utilize both stem cell and biomaterials for the treatment of skeletal muscle injury and disease is discussed.
Journal ArticleDOI
Adipogenesis of skeletal muscle fibro/adipogenic progenitors is affected by the WNT5a/GSK3/β-catenin axis
Alessio Reggio,Marco Rosina,Alessandro Palma,Andrea Cerquone Perpetuini,Lucia Lisa Petrilli,Cesare Gargioli,Claudia Fuoco,Elisa Micarelli,Giulio Giuliani,Mauro Cerretani,Alberto Bresciani,Francesca Sacco,Luisa Castagnoli,Gianni Cesareni +13 more
TL;DR: FAPs are characterized as the main source of WNT ligands inferring their potential in mediating autocrine/paracrine responses in the muscle niche, and WNT5a, whose expression is impaired in dystrophic FAPs, is identified as a crucial W NT ligand able to restrain the detrimental adipogenic differentiation drift of these cells through the positive modulation of the β-catenin signaling.
Journal ArticleDOI
Evolving Roles of Muscle-Resident Fibro-Adipogenic Progenitors in Health, Regeneration, Neuromuscular Disorders, and Aging.
TL;DR: In this article, a review of the current knowledge of fibro-adipogenic progenitor function on muscle homeostatic integrity, regeneration, repair, and aging is presented.
References
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Muscle injury activates resident fibro/adipogenic progenitors that facilitate myogenesis
Aaron W. Joe,Lin Yi,Anuradha Natarajan,Fabien Le Grand,Leslie So,Joy X. Wang,Michael A. Rudnicki,Fabio M.V. Rossi +7 more
TL;DR: A new subpopulation of fibro/adipogenic progenitors (FAPs) resident in muscle tissue but arising from a distinct developmental lineage is described, which expand upon damage to provide a transient source of pro-differentiation signals for proliferating myogenic progensitors.
Journal ArticleDOI
Mesenchymal progenitors distinct from satellite cells contribute to ectopic fat cell formation in skeletal muscle.
TL;DR: It is suggested that interaction between muscle cells and PDGFRα+ mesenchymal progenitors, not the fate decision of satellite cells, has a considerable impact on muscle homeostasis and is the major contributor to ectopic fat cell formation in skeletal muscle.
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Fatty Infiltration and Atrophy of the Rotator Cuff Do Not Improve After Rotator Cuff Repair and Correlate With Poor Functional Outcome
TL;DR: It is suggested that repairs should be performed, if possible, before more significant deterioration in the cuff musculature in order to optimize outcomes, and that understanding the degree of muscle atrophy and fatty infiltration before surgery can help guide patient expectations.
Journal ArticleDOI
Type 2 innate signals stimulate fibro/adipogenic progenitors to facilitate muscle regeneration.
Jose E. Heredia,Lata Mukundan,Francis M. Chen,Alisa A. Mueller,Rahul C. Deo,Richard M. Locksley,Thomas A. Rando,Thomas A. Rando,Ajay Chawla +8 more
TL;DR: It is demonstrated that type 2 innate immunity is required for regeneration of skeletal muscle after injury and type 2 cytokine signaling is also required in FAPs, but not in myeloid cells, for rapid clearance of necrotic debris, a process that is necessary for timely and complete regeneration of tissues.
Journal ArticleDOI
Nilotinib reduces muscle fibrosis in chronic muscle injury by promoting TNF-mediated apoptosis of fibro/adipogenic progenitors
Dario R. Lemos,Farshad Babaeijandaghi,Marcela Low,ChihKai Chang,Sunny Lee,Daniela Fiore,Regan-Heng Zhang,Anuradha Natarajan,Sergei A. Nedospasov,Fabio M.V. Rossi +9 more
TL;DR: The findings reveal an unexpected anti-fibrotic role of TNF and suggest that disruption of the precisely timed progression from a TNF-rich to a TGF-β−rich environment favors fibrotic degeneration of the muscle during chronic injury.