ArticleCell communication and signaling : CCS2021
Perturbation of PI3K/Akt signaling affected autophagy modulation in dystrophin-deficient myoblasts.
Article in Cell communication and signaling : CCS, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- ANXA11 suppression restores muscular function in the mdx mouse model of Duchenne muscular dystrophy (DMD).Nature communications · 2026Article
- Impaired stem cell migration and divisions in Duchenne muscular dystrophy revealed by live imaging.Nature communications · 2026Article
- Emerging therapeutic strategies in muscular dystrophy: an updated review on pathogenesis and treatment advances.Molecular biology reports · 2026Review
- A review: oxidative stress in skeletal muscle and the non-coding RNAs behind it.Molecular and cellular biochemistry · 2025Review
- Integrative Approaches to Myopathies and Muscular Dystrophies: Molecular Mechanisms, Diagnostics, and Future Therapies.International journal of molecular sciences · 2025Review
- Extracellular matrix: Dystroglycan interactions-Roles for the dystrophin-associated glycoprotein complex in skeletal tissue dynamics.International journal of experimental pathology · 2025Review
- Stem/progenitor cell-based therapy for Duchenne muscular dystrophy.Frontiers in cell and developmental biology · 2025Review
- Interconnection of CD133 Stem Cell Marker with Autophagy and Apoptosis in Colorectal Cancer.International journal of molecular sciences · 2024Review
- The Role of MicroRNA in the Pathogenesis of Duchenne Muscular Dystrophy.International journal of molecular sciences · 2024Review
- Integrated analysis of the DNA methylome and RNA transcriptome during the development of skeletal muscle in Duroc pigs.BMC genomics · 2024Article
- Diverse WGBS profiles of longissimus dorsi muscle in Hainan black goats and hybrid goats.BMC genomic data · 2023Article
- The Role of P2X7 Purinoceptors in the Pathogenesis and Treatment of Muscular Dystrophies.International journal of molecular sciences · 2023Review
- Modelling Skeletal Muscle Ageing and RepairJournal of tissue engineering and regenerative medicine · 2023Article
- A deep redox proteome profiling workflow and its application to skeletal muscle of a Duchenne Muscular Dystrophy model.Free radical biology & medicine · 2022Article
- IFN-τ mediated miR-26a targeting PTEN to activate PI3K/AKT signalling to alleviate the inflammatory damage of bEECs.Scientific reports · 2022Article
- Torin1 restores proliferation rate in Charcot-Marie-Tooth disease type 2A cells harbouring MFN2 (mitofusin 2) mutation.Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology · 2022Article
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Authors and funding
2 authors at 2 institutions in 3 countries.
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Abstract
backgroundThe absence of dystrophin has gave a massive impact on myotube development in Muscular Dystrophy pathogenesis. One of the conserved signaling pathways involved in skeletal muscle differentiation is the PI3K/Akt/mTOR pathway that plays a vital role in autophagy regulation. To further understand and establish targeted therapy in dystrophin-deficient myoblasts, protein expression profiling has been determined which provides information on perturbed autophagy modulation and activation.
methodsIn this study, a dystrophin-deficient myoblast cell line established from the skeletal muscle of a dystrophic (mdx) mouse was used as a model. The dfd13 (dystrophin-deficient) and C2C12 (non-dystrophic) myoblasts were cultured in low mitogen conditions for 10 days to induce differentiation. The cells were subjected to total protein extraction prior to Western blotting assay technique. Protein sub-fractionation has been conducted to determine protein localization. The live-cell analysis of autophagy assay was done using a flow cytometer.
resultsIn our culture system, the dfd13 myoblasts did not achieve terminal differentiation. PTEN expression was profoundly increased in dfd13 myoblasts throughout the differentiation day subsequently indicates perturbation of PI3K/Akt/mTOR regulation. In addition, rictor-mTORC2 was also found inactivated in this event. This occurrence has caused FoxO3 misregulation leads to higher activation of autophagy-related genes in dfd13 myoblasts. Autophagosome formation was increased as LC3B-I/II showed accumulation upon differentiation. However, the ratio of LC3B lipidation and autophagic flux were shown decreased which exhibited dystrophic features.
conclusionPerturbation of the PTEN-PI3K/Akt pathway triggers excessive autophagosome formation and subsequently reduced autophagic flux within dystrophin-deficient myoblasts where these findings are of importance to understand Duchenne Muscular Dystrophy (DMD) patients. We believe that some manipulation within its regulatory signaling reported in this study could help restore muscle homeostasis and attenuate disease progression. Video Abstract.
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