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  1. Article ; Online: Depletion of SMN protein in mesenchymal progenitors impairs the development of bone and neuromuscular junction in spinal muscular atrophy.

    Hann, Sang-Hyeon / Kim, Seon-Yong / Kim, Ye Lynne / Jo, Young-Woo / Kang, Jong-Seol / Park, Hyerim / Choi, Se-Young / Kong, Young-Yun

    eLife

    2024  Volume 12

    Abstract: Spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by the deficiency of the survival motor neuron (SMN) protein, which leads to motor neuron dysfunction and muscle atrophy. In addition to the requirement for SMN in motor neurons, ... ...

    Abstract Spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by the deficiency of the survival motor neuron (SMN) protein, which leads to motor neuron dysfunction and muscle atrophy. In addition to the requirement for SMN in motor neurons, recent studies suggest that SMN deficiency in peripheral tissues plays a key role in the pathogenesis of SMA. Using limb mesenchymal progenitor cell (MPC)-specific SMN-depleted mouse models, we reveal that SMN reduction in limb MPCs causes defects in the development of bone and neuromuscular junction (NMJ). Specifically, these mice exhibited impaired growth plate homeostasis and reduced insulin-like growth factor (IGF) signaling from chondrocytes, rather than from the liver. Furthermore, the reduction of SMN in fibro-adipogenic progenitors (FAPs) resulted in abnormal NMJ maturation, altered release of neurotransmitters, and NMJ morphological defects. Transplantation of healthy FAPs rescued the morphological deterioration. Our findings highlight the significance of mesenchymal SMN in neuromusculoskeletal pathogenesis of SMA and provide insights into potential therapeutic strategies targeting mesenchymal cells for the treatment of SMA.
    MeSH term(s) Animals ; Mice ; Disease Models, Animal ; Motor Neurons/physiology ; Muscular Atrophy, Spinal/genetics ; Muscular Atrophy, Spinal/metabolism ; Neuromuscular Diseases/pathology ; Neuromuscular Junction/metabolism ; Transcription Factors/metabolism ; Survival of Motor Neuron 1 Protein/genetics ; Survival of Motor Neuron 1 Protein/metabolism
    Chemical Substances Transcription Factors ; Smn1 protein, mouse ; Survival of Motor Neuron 1 Protein
    Language English
    Publishing date 2024-02-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.92731
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Improved therapeutic approach for spinal muscular atrophy via ubiquitination-resistant survival motor neuron variant.

    Rhee, Joonwoo / Kang, Jong-Seol / Jo, Young-Woo / Yoo, Kyusang / Kim, Ye Lynne / Hann, Sang-Hyeon / Kim, Yea-Eun / Kim, Hyun / Kim, Ji-Hoon / Kong, Young-Yun

    Journal of cachexia, sarcopenia and muscle

    2024  

    Abstract: Background: Zolgensma is a gene-replacement therapy that has led to a promising treatment for spinal muscular atrophy (SMA). However, clinical trials of Zolgensma have raised two major concerns: insufficient therapeutic effects and adverse events. In a ... ...

    Abstract Background: Zolgensma is a gene-replacement therapy that has led to a promising treatment for spinal muscular atrophy (SMA). However, clinical trials of Zolgensma have raised two major concerns: insufficient therapeutic effects and adverse events. In a recent clinical trial, 30% of patients failed to achieve motor milestones despite pre-symptomatic treatment. In addition, more than 20% of patients showed hepatotoxicity due to excessive virus dosage, even after the administration of an immunosuppressant. Here, we aimed to test whether a ubiquitination-resistant variant of survival motor neuron (SMN), SMN
    Methods: A severe SMA mouse model, SMA type 1.5 (Smn
    Results: AAV9-SMN
    Conclusions: SMN
    Language English
    Publishing date 2024-04-22
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2586864-0
    ISSN 2190-6009 ; 2190-5991
    ISSN (online) 2190-6009
    ISSN 2190-5991
    DOI 10.1002/jcsm.13486
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Notch1 and Notch2 Signaling Exclusively but Cooperatively Maintain Fetal Myogenic Progenitors.

    Jo, Young-Woo / Park, Inkuk / Yoo, Kyusang / Woo, Hyun-Young / Kim, Ye Lynne / Kim, Yea-Eun / Kim, Ji-Hoon / Kong, Young-Yun

    Stem cells (Dayton, Ohio)

    2022  Volume 40, Issue 11, Page(s) 1031–1042

    Abstract: Myogenic progenitors (MPs) generate myocytes that fuse to form myofibers during skeletal muscle development while maintaining the progenitor pool, which is crucial for generating sufficient muscle. Notch signaling has been known to reserve a population ... ...

    Abstract Myogenic progenitors (MPs) generate myocytes that fuse to form myofibers during skeletal muscle development while maintaining the progenitor pool, which is crucial for generating sufficient muscle. Notch signaling has been known to reserve a population of embryonic MPs during primary myogenesis by promoting cell cycle exit and suppressing premature differentiation. However, the roles of individual Notch receptors (Notch1-4) during embryonic/fetal myogenesis are still elusive. In this study, we found that Notch1 and Notch2, which exhibit the highest structural similarity among Notch receptors, maintain the MP population by distinct mechanisms: Notch1 induces cell cycle exit and Notch2 suppresses premature differentiation. Moreover, genetic and cell culture studies showed that Notch1 and Notch2 signaling in MPs are distinctively activated by interacting with Notch ligand-expressing myofibers and MP-lineage cells, respectively. These results suggest that through different activation modes, Notch1 and Notch2 distinctively and cooperatively maintain MP population during fetal myogenesis for proper muscle development.
    MeSH term(s) Receptor, Notch1/genetics ; Receptor, Notch1/metabolism ; Muscle Development/genetics ; Signal Transduction/physiology ; Cell Differentiation/genetics ; Receptors, Notch
    Chemical Substances Receptor, Notch1 ; Receptors, Notch
    Language English
    Publishing date 2022-08-03
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1143556-2
    ISSN 1549-4918 ; 1066-5099
    ISSN (online) 1549-4918
    ISSN 1066-5099
    DOI 10.1093/stmcls/sxac056
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1894: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: Baf155 regulates skeletal muscle metabolism via HIF-1a signaling.

    Kang, Jong-Seol / Kim, Dongha / Rhee, Joonwoo / Seo, Ji-Yun / Park, Inkuk / Kim, Ji-Hoon / Lee, Daewon / Lee, WonUk / Kim, Ye Lynne / Yoo, Kyusang / Bae, Sunghwan / Chung, Jongkyeong / Seong, Rho Hyun / Kong, Young-Yun

    PLoS biology

    2023  Volume 21, Issue 7, Page(s) e3002192

    Abstract: During exercise, skeletal muscle is exposed to a low oxygen condition, hypoxia. Under hypoxia, the transcription factor hypoxia-inducible factor-1α (HIF-1α) is stabilized and induces expressions of its target genes regulating glycolytic metabolism. Here, ...

    Abstract During exercise, skeletal muscle is exposed to a low oxygen condition, hypoxia. Under hypoxia, the transcription factor hypoxia-inducible factor-1α (HIF-1α) is stabilized and induces expressions of its target genes regulating glycolytic metabolism. Here, using a skeletal muscle-specific gene ablation mouse model, we show that Brg1/Brm-associated factor 155 (Baf155), a core subunit of the switch/sucrose non-fermentable (SWI/SNF) complex, is essential for HIF-1α signaling in skeletal muscle. Muscle-specific ablation of Baf155 increases oxidative metabolism by reducing HIF-1α function, which accompanies the decreased lactate production during exercise. Furthermore, the augmented oxidation leads to high intramuscular adenosine triphosphate (ATP) level and results in the enhancement of endurance exercise capacity. Mechanistically, our chromatin immunoprecipitation (ChIP) analysis reveals that Baf155 modulates DNA-binding activity of HIF-1α to the promoters of its target genes. In addition, for this regulatory function, Baf155 requires a phospho-signal transducer and activator of transcription 3 (pSTAT3), which forms a coactivator complex with HIF-1α, to activate HIF-1α signaling. Our findings reveal the crucial role of Baf155 in energy metabolism of skeletal muscle and the interaction between Baf155 and hypoxia signaling.
    MeSH term(s) Animals ; Mice ; Gene Expression Regulation ; Hypoxia/metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Muscle, Skeletal/metabolism ; Signal Transduction ; Transcription Factors/genetics ; Transcription Factors/metabolism
    Chemical Substances Hypoxia-Inducible Factor 1, alpha Subunit ; Transcription Factors ; Smarcc1 protein, mouse
    Language English
    Publishing date 2023-07-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2126776-5
    ISSN 1545-7885 ; 1544-9173
    ISSN (online) 1545-7885
    ISSN 1544-9173
    DOI 10.1371/journal.pbio.3002192
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6193: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  5. Article ; Online: Maintenance of type 2 glycolytic myofibers with age by Mib1-Actn3 axis.

    Seo, Ji-Yun / Kang, Jong-Seol / Kim, Ye Lynne / Jo, Young-Woo / Kim, Ji-Hoon / Hann, Sang-Hyeon / Park, Jieon / Park, Inkuk / Park, Hyerim / Yoo, Kyusang / Rhee, Joonwoo / Park, Jung-Wee / Ha, Yong Chan / Kong, Young-Yun

    Nature communications

    2021  Volume 12, Issue 1, Page(s) 1294

    Abstract: Age-associated muscle atrophy is a debilitating condition associated with loss of muscle mass and function with age that contributes to limitation of mobility and locomotion. However, the underlying mechanisms of how intrinsic muscle changes with age are ...

    Abstract Age-associated muscle atrophy is a debilitating condition associated with loss of muscle mass and function with age that contributes to limitation of mobility and locomotion. However, the underlying mechanisms of how intrinsic muscle changes with age are largely unknown. Here we report that, with age, Mind bomb-1 (Mib1) plays important role in skeletal muscle maintenance via proteasomal degradation-dependent regulation of α-actinin 3 (Actn3). The disruption of Mib1 in myofibers (Mib1
    MeSH term(s) Actinin/genetics ; Actinin/metabolism ; Aging/genetics ; Aging/physiology ; Animals ; Gene Expression Regulation ; Genotype ; HEK293 Cells ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Muscle, Skeletal/metabolism ; Proteasome Endopeptidase Complex ; Transcriptome ; Ubiquitin-Protein Ligases/genetics ; Ubiquitin-Protein Ligases/metabolism
    Chemical Substances ACTN3 protein, human ; Actn3 protein, mouse ; Actinin (11003-00-2) ; MIB1 protein, mouse (EC 2.3.2.27) ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; Proteasome Endopeptidase Complex (EC 3.4.25.1)
    Language English
    Publishing date 2021-02-26
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-021-21621-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: The hypothalamic-pituitary-gonadal axis controls muscle stem cell senescence through autophagosome clearance.

    Kim, Ji-Hoon / Park, Inkuk / Shin, Hijai R / Rhee, Joonwoo / Seo, Ji-Yun / Jo, Young-Woo / Yoo, Kyusang / Hann, Sang-Hyeon / Kang, Jong-Seol / Park, Jieon / Kim, Ye Lynne / Moon, Ju-Yeon / Choi, Man Ho / Kong, Young-Yun

    Journal of cachexia, sarcopenia and muscle

    2020  Volume 12, Issue 1, Page(s) 177–191

    Abstract: Background: With organismal aging, the hypothalamic-pituitary-gonadal (HPG) activity gradually decreases, resulting in the systemic functional declines of the target tissues including skeletal muscles. Although the HPG axis plays an important role in ... ...

    Abstract Background: With organismal aging, the hypothalamic-pituitary-gonadal (HPG) activity gradually decreases, resulting in the systemic functional declines of the target tissues including skeletal muscles. Although the HPG axis plays an important role in health span, how the HPG axis systemically prevents functional aging is largely unknown.
    Methods: We generated muscle stem cell (MuSC)-specific androgen receptor (Ar) and oestrogen receptor 2 (Esr2) double knockout (dKO) mice and pharmacologically inhibited (Antide) the HPG axis to mimic decreased serum levels of sex steroid hormones in aged mice. After short-term and long-term sex hormone signalling ablation, the MuSCs were functionally analysed, and their aging phenotypes were compared with those of geriatric mice (30-month-old). To investigate pathways associated with sex hormone signalling disruption, RNA sequencing and bioinformatic analyses were performed.
    Results: Disrupting the HPG axis results in impaired muscle regeneration [wild-type (WT) vs. dKO, P < 0.0001; Veh vs. Antide, P = 0.004]. The expression of DNA damage marker (in WT = 7.0 ± 1.6%, dKO = 32.5 ± 2.6%, P < 0.01; in Veh = 13.4 ± 4.5%, Antide = 29.7 ± 5.5%, P = 0.028) and senescence-associated β-galactosidase activity (in WT = 3.8 ± 1.2%, dKO = 10.3 ± 1.6%, P < 0.01; in Veh = 2.1 ± 0.4%, Antide = 9.6 ± 0.8%, P = 0.005), as well as the expression levels of senescence-associated genes, p16
    Conclusions: Our data show that the HPG axis systemically controls autophagosome clearance in MuSCs through Tfeb and prevents MuSCs from senescence, suggesting that sustained HPG activity throughout life regulates autophagosome clearance to maintain the quiescence of MuSCs by preventing senescence until advanced age.
    MeSH term(s) Animals ; Autophagosomes ; Cellular Senescence ; Gonads ; Hypothalamus ; Mice ; Muscle, Skeletal ; Myoblasts ; Pituitary Gland ; Regeneration ; Stem Cells
    Language English
    Publishing date 2020-11-27
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2586864-0
    ISSN 2190-6009 ; 2190-5991
    ISSN (online) 2190-6009
    ISSN 2190-5991
    DOI 10.1002/jcsm.12653
    Database MEDical Literature Analysis and Retrieval System OnLINE

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