The INSR/AKT/mTOR pathway regulates the pace of myogenesis in a syndecan-3-dependent manner

Jones, Fiona K.; Jones, Andrew R.; Pisconti, Addolorata

doi:10.1016/j.matbio.2022.09.004

Cited by 4 publications

(1 citation statement)

References 76 publications

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“…Syndecans are involved in several signaling pathways, including ERK/MAPK ( Hara et al, 2021 ), AKT/mTOR/S6K1, and Wnt signaling ( Luyten et al, 2008 ; Jones et al, 2020 ; Hara et al, 2021 ; Johnson de Sousa Brito et al, 2021 ; Jones et al, 2022 ); however, none of them have previously been investigated in the context of WB myopathy.…”

Section: Discussionmentioning

confidence: 99%

Characterization of wooden breast myopathy: a focus on syndecans and ECM remodeling

Pejšková,

Rønning,

Kent

et al. 2023

Front. Physiol.

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Introduction: The skeletal muscle deformity of commercial chickens (Gallus gallus), known as the wooden breast (WB), is associated with fibrotic myopathy of unknown etiology. For future breeding strategies and genetic improvements, it is essential to identify the molecular mechanisms underlying the phenotype. The pathophysiological hallmarks of WB include severe skeletal muscle fibrosis, inflammation, myofiber necrosis, and multifocal degeneration of muscle tissue. The transmembrane proteoglycans syndecans have a wide spectrum of biological functions and are master regulators of tissue homeostasis. They are upregulated and shed (cleaved) as a regulatory mechanism during tissue repair and regeneration. During the last decades, it has become clear that the syndecan family also has critical functions in skeletal muscle growth, however, their potential involvement in WB pathogenesis is unknown.Methods: In this study, we have categorized four groups of WB myopathy in broiler chickens and performed a comprehensive characterization of the molecular and histological profiles of two of them, with a special focus on the role of the syndecans and remodeling of the extracellular matrix (ECM).Results and discussion: Our findings reveal differential expression and shedding of the four syndecan family members and increased matrix metalloproteinase activity. Additionally, we identified alterations in key signaling pathways such as MAPK, AKT, and Wnt. Our work provides novel insights into a deeper understanding of WB pathogenesis and suggests potential therapeutic targets for this condition.

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Section: Discussionmentioning

confidence: 99%

Characterization of wooden breast myopathy: a focus on syndecans and ECM remodeling

Pejšková,

Rønning,

Kent

et al. 2023

Front. Physiol.

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Circular RNAs and host genes act synergistically in regulating cellular processes and functions in skeletal myogenesis

Huang,

Choo

2024

Gene

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Wooden breast myopathy is characterized by satellite cell dysfunction and syndecan-4 shedding

Pejšková,

Pisconti,

Lunde

et al. 2024

Front. Physiol.

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IntroductionSkeletal muscle satellite cells (MuSCs or stem cells) play a crucial role in muscle development, maintenance, and regeneration, supporting both hypertrophy and regenerative myogenesis. Syndecans (SDCs) act as communication bridges within the muscle microenvironment, regulating interactions with extracellular matrix components and contributing significantly to tissue repair and inflammation. Specifically, syndecan-4 (SDC4) is involved in muscle regeneration at multiple stages.MethodsThis study delves into the emerging challenge of wooden breast (WB) myopathy and its connection with SDC4. Our hypothesis proposes that disruptions in MuSC dynamics through SDC4 contribute to the increased incidence of breast myopathies observed in growing broilers. To test our hypothesis, non-affected and affected broilers were systematically selected, and the characteristics of WB myopathy were studied both in vitro and in vivo. SDC4 overexpression in MuSCs and blocking peptides (BPs) corresponding to the SDC4 ectodomain were used for investigating the role of SDC4 in muscle development and its shedding levels.Results and discussionIn vivo examination of affected muscles revealed smaller fibers and changes in metabolic pathways. In vitro studies unveiled disrupted proliferation of MuSCs in WB myopathy, accompanied by the downregulation of several muscle markers. Investigation of the potential role of SDC4 in the pathogenesis of WB myopathy revealed a decreased tendency in SDC4 gene expression and increased shedding of its ectodomain. Moreover, we showed that SDC4 overexpression is linked to reduced proliferation in MuSCs and affected myogenesis. We detected an impaired proliferation of WB-affected MuSCs, revealing critical insights into the dysfunctional state of these cells in myopathy. Additionally, by treating MuSCs with blocking peptides derived from the SDC4 ectodomain, we identified altered proliferation. Taken together, this work contributes with valuable knowledge on the molecular mechanisms underlying WB myopathy and the role of SDC4 in this chicken myopathy.

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The INSR/AKT/mTOR pathway regulates the pace of myogenesis in a syndecan-3-dependent manner

Cited by 4 publications

References 76 publications

Characterization of wooden breast myopathy: a focus on syndecans and ECM remodeling

Characterization of wooden breast myopathy: a focus on syndecans and ECM remodeling

Circular RNAs and host genes act synergistically in regulating cellular processes and functions in skeletal myogenesis

Wooden breast myopathy is characterized by satellite cell dysfunction and syndecan-4 shedding

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