In Vivo Activation of STAT3 Signaling in Satellite Cells and Myofibers in Regenerating Rat Skeletal Muscles

Kami, Katsuya; Senba, Emiko

doi:10.1177/002215540205001202

Cited by 85 publications

(85 citation statements)

References 63 publications

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“…However, despite the fact that these signal transduction pathways are involved in regulating cell proliferation (33), we did not find that LIF had any effect on the proliferation of rhabdomyosarcoma cell lines. This is in striking contrast to normal skeletal muscle cells where LIF has been reported to act as a proliferative factor (33).…”

Section: Discussioncontrasting

confidence: 59%

Leukemia Inhibitory Factor: A Newly Identified Metastatic Factor in Rhabdomyosarcomas

Wysoczynski

Miękus²,

Jankowski³

et al. 2007

Cancer Research

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Rhabdomyosarcoma frequently infiltrates bone marrow and this process involves the stromal-derived factor-1 (SDF-1)-CXCR4 axis. Because leukemia inhibitory factor (LIF), like SDF-1, is secreted by bone marrow stroma and directs the regeneration of skeletal muscles, we examined whether the LIF-LIF receptor (LIF-R) axis affects the biology of rhabdomyosarcoma cells. We found that in rhabdomyosarcoma cells, LIF stimulates the following: (a) phosphorylation of mitogenactivated protein kinase p42/44, AKT, and signal transducers and activators of transcription 3, (b) adhesion and chemotaxis, and (c) increased resistance to cytostatics. To compare the biological effects of LIF versus SDF-1, we examined the RH30 cell line, which is highly responsive to both ligands, and found that the chemotaxis of these cells is significantly reduced when the inhibitors of both receptors (T140 for CXCR4 and gp190 blocking antibody for LIF-R) are added simultaneously. Subsequently, by using repetitive chemotaxis to LIF or SDF-1, we selected from the RH30 line subpopulations of cells that respond to LIF but not SDF-1 (RH30-L) or to SDF-1 but not LIF (RH30-S). We found that (a) RH30-L cells seed better to the bone marrow, liver, and lymph nodes of immunodeficient mice than RH30-S cells and (b) mice inoculated i.m. with the RH30-L cells had more rhabdomyosarcoma cells in the bone marrow and lung after 6 weeks. Thus, we present the first evidence that the LIF-LIF-R axis may direct rhabdomyosarcoma metastasis. Further, because we showed that the in vivo metastasis of RH30 cells is inhibited by small interfering RNA against LIF-R, molecular targeting of this axis could become a new strategy to control the metastasis of rhabdomyosarcoma. [Cancer Res 2007;67(5):2131-40]

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Section: Discussioncontrasting

confidence: 59%

Leukemia Inhibitory Factor: A Newly Identified Metastatic Factor in Rhabdomyosarcomas

Wysoczynski

Miękus²,

Jankowski³

et al. 2007

Cancer Research

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“…The HGF receptor c-met is expressed in both quiescent and activated SCs (3,23,43) and is an early-immediate gene in SC activation (94). The in situ hybridization protocol was carried out as reported, to visualize c-met transcript expression in individual SCs in sections with a probe and color detection methods previously reported (8,96).…”

Section: Methodsmentioning

confidence: 99%

Nitric oxide donors improve prednisone effects on muscular dystrophy in the mdx mouse diaphragm

Mizunoya¹,

Upadhaya²,

Burczynski

et al. 2011

American Journal of Physiology-Cell Physiology

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Mizunoya W, Upadhaya R, Burczynski FJ, Wang G, Anderson JE. Nitric oxide donors improve prednisone effects on muscular dystrophy in the mdx mouse diaphragm. Am J Physiol Cell Physiol 300: C1065-C1077, 2011. First published January 26, 2011 doi:10.1152/ajpcell.00482.2010.-In Duchenne muscular dystrophy (DMD), palliative glucocorticoid therapy can produce myopathy or calcification. Since increased nitric oxide synthase activity in dystrophic mice promotes regeneration, the outcome of two nitric oxide (NO) donor drugs, MyoNovin (M) and isosorbide dinitrate (I), on the effectiveness of the anti-inflammatory drug prednisone (P) in alleviating progression of dystrophy was tested. Dystrophic mdx mice were treated (18 days) as controls or with an NO donor Ϯ P. Fiber permeability and DNA synthesis were labeled by Evans blue dye (EBD) and bromodeoxyuridine uptake, respectively. P decreased body weight gain, M increased quadriceps mass, and I increased heart mass. P increased fiber permeability (%EBDϩ fibers) and calcification in diaphragm. Treatment with NO donors ϩ P (MϩP, IϩP) reduced %EBDϩ fibers and calcification vs. P alone. %EBDϩ fibers in MϩP diaphragm did not differ from control. NO donor treatment reduced proliferation and the population of c-metϩ cells and accelerated fiber regeneration. Concurrent with P, NO donor treatment suppressed two important detrimental effects of P in mice, possibly by accelerating regeneration, rebalancing satellite cell quiescence and activation in dystrophy, and/or increasing perfusion. Results suggest that NO donors could improve current therapy for DMD.Duchenne muscular dystrophy; skeletal muscle; satellite cells; glucocorticoid MUSCULAR DYSTROPHIES are lethal genetic muscle diseases, and the most common form, Duchenne muscular dystrophy (DMD), is caused by mutation in the dystrophin gene (37). Absence of dystrophin from the cytoskeleton in DMD fibers leads to disruption of the sarcolemma by mechanical stress or exercise and progressive muscle weakness and wasting (20,27,56,69). Investigations of possible therapeutic interventions using the mdx mouse model of DMD have examined gene therapy by viral delivery of full-length dystrophin (28) or microdystrophin (97), stem (satellite) cell transplantation (40), and read-through (91) or exon-skipping approaches (2, 55, 93) to restore dystrophin expression. As these investigations are ongoing, pharmacological treatment with glucocorticoids remains the current "gold standard" therapy in DMD.Treatment with prednisone promotes a palliative reduction in inflammation and delays disease progression (57, 58) in DMD. In DMD patients and mdx mice, prednisone and deflazacort reduce the secondary inflammation that extends muscle fiber necrosis outside the region of primary damage that is caused by exercise-induced membrane breaks or eccentric contraction (25, 63). In addition, deflazacort also upregulates the calcineurin/nuclear factor of activated T cells (NFAT) pathway activity, which counteracts the muscle-specific activation of JNK1 that damages...

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“…[51][52][53] STAT3 is a transcription factor essential for embryonic stem cell pluripotency, 54,55 and STAT3 signaling may also be activated in skeletal muscle after acute exercise or injury. 56,57 Moreover, STAT3 may be one of the downstream factors of Notch1 (Notch1-STAT3 signaling), which regulate stem cell characteristics. 58 Msx1 is a critical regulator of muscle development and regeneration that is primarily expressed in animals in the embryonic or fetal stage and is able to repress myogenic differentiation and maintain the undifferentiated status of stem cells.…”

Section: Discussionmentioning

confidence: 99%

“…66,68 Up-regulated Notch1 and STAT3 signaling may contribute to improved proliferation capacity and multipotency of SASCs from injured muscle because both Notch1 and STAT3 are involved in stem cell maintenance and self-renewal. 54,55,58,69,70 Activation of Notch1 and STAT3 signaling pathways is also required for efficient muscle regeneration, 51,57 and their activation in SASCs from injured muscle may verify the highly regenerative potential and important function of this specific cell population in repairing injured muscle. In addition, the finding of activated Notch1 signaling in SASCs may suggest a promising contribution of the cells in therapeutic applications for regeneration of aged skeletal muscle.…”

Section: Discussionmentioning

confidence: 99%

Slow-Adhering Stem Cells Derived from Injured Skeletal Muscle Have Improved Regenerative Capacity

Xiang

Rathbone

et al. 2011

The American Journal of Pathology

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A wide variety of myogenic cell sources have been used for repair of injured and diseased muscle including muscle stem cells, which can be isolated from skeletal muscle as a group of slow-adhering cells on a collagen-coated surface. The therapeutic use of muscle stem cells for improving muscle regeneration is promising; however, the effect of injury on their characteristics and engraftment potential has yet to be described. In the present study, slow-adhering stem cells (SASCs) from both laceration-injured and control noninjured skeletal muscles in mice were isolated and studied. Migration and proliferation rates, multidifferentiation potentials, and differences in gene expression in both groups of cells were compared in vitro. Results demonstrated that a larger population of SASCs could be isolated from injured muscle than from control noninjured muscle. In addition, SASCs derived from injured muscle demonstrated improved migration, a higher rate of proliferation and multidifferentiation, and increased expression of Notch1, STAT3, Msx1, and MMP2. Moreover, when transplanted into dystrophic muscle in MDX/SCID mice, SASCs from injured muscle generated greater engraftments with a higher capillary density than did SASCs from control noninjured muscle. These data suggest that traumatic injury may modify stem cell characteristics through trophic factors and improve the transplantation potential of SASCs in alleviating skeletal muscle injuries and diseases.

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In Vivo Activation of STAT3 Signaling in Satellite Cells and Myofibers in Regenerating Rat Skeletal Muscles

Cited by 85 publications

References 63 publications

Leukemia Inhibitory Factor: A Newly Identified Metastatic Factor in Rhabdomyosarcomas

Leukemia Inhibitory Factor: A Newly Identified Metastatic Factor in Rhabdomyosarcomas

Nitric oxide donors improve prednisone effects on muscular dystrophy in the mdx mouse diaphragm

Slow-Adhering Stem Cells Derived from Injured Skeletal Muscle Have Improved Regenerative Capacity

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