Dataset Information

NRF2 Regulates Viability, Proliferation, Resistance to Oxidative Stress, and Differentiation of Murine Myoblasts and Muscle Satellite Cells.

ABSTRACT: Increased oxidative stress can slow down the regeneration of skeletal muscle and affect the activity of muscle satellite cells (mSCs). Therefore, we evaluated the role of the NRF2 transcription factor (encoded by the Nfe2l2 gene), the main regulator of the antioxidant response, in muscle cell biology. We used (i) an immortalized murine myoblast cell line (C2C12) with stable overexpression of NRF2 and (ii) primary mSCs isolated from wild-type and Nfe2l2 (transcriptionally)-deficient mice (Nfe2l2^tKO). NRF2 promoted myoblast proliferation and viability under oxidative stress conditions and decreased the production of reactive oxygen species. Furthermore, NRF2 overexpression inhibited C2C12 cell differentiation by down-regulating the expression of myogenic regulatory factors (MRFs) and muscle-specific microRNAs. We also showed that NRF2 is indispensable for the viability of mSCs since the lack of its transcriptional activity caused high mortality of cells cultured in vitro under normoxic conditions. Concomitantly, Nfe2l2^tKO mSCs grown and differentiated under hypoxic conditions were viable and much more differentiated compared to cells isolated from wild-type mice. Taken together, NRF2 significantly influences the properties of myoblasts and muscle satellite cells. This effect might be modulated by the muscle microenvironment.

SUBMITTER: Bronisz-Budzynska I

PROVIDER: S-EPMC9600498 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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NRF2 Regulates Viability, Proliferation, Resistance to Oxidative Stress, and Differentiation of Murine Myoblasts and Muscle Satellite Cells.

Bronisz-Budzyńska Iwona I Kozakowska Magdalena M Pietraszek-Gremplewicz Katarzyna K Madej Magdalena M Józkowicz Alicja A Łoboda Agnieszka A Dulak Józef J

Cells 20221021 20

Increased oxidative stress can slow down the regeneration of skeletal muscle and affect the activity of muscle satellite cells (mSCs). Therefore, we evaluated the role of the NRF2 transcription factor (encoded by the <i>Nfe2l2</i> gene), the main regulator of the antioxidant response, in muscle cell biology. We used (i) an immortalized murine myoblast cell line (C2C12) with stable overexpression of NRF2 and (ii) primary mSCs isolated from wild-type and <i>Nfe2l2</i> (transcriptionally)-deficient ...[more]

PMID: 36291188

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Project description:ObjectiveAsparagine synthetase (ASNS) is an aminotransferase responsible for the biosynthesis of aspartate by using aspartic acid and glutamine. ASNS is highly expressed in fast-growing broilers, but few studies have reported the regulatory role of ASNS in muscle development.MethodsTo explore the function of ASNS in chicken muscle development, the expression of ASNS in different chicken breeds and tissues were first performed by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR). Then, using real-time quantitative RT-PCR, western blot, EdU assay, cell cycle assay and immunofluorescence, the effects of ASNS on the proliferation and differentiation of chicken skeletal muscle satellite cell (SMSC) were investigated. Finally, potential mechanisms by which ASNS influences chicken muscle fiber differentiation were identified through RNA-Seq.ResultsThe mRNA expression pattern of ASNS in muscles mirrors trends in muscle fiber cross-sectional area, average daily weight gain, and muscle weight across different breeds. ASNS knockdown inhibited SMSC proliferation, while overexpression showed the opposite. Moreover, ASNS attenuated SMSC differentiation by activating the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathway. Additionally, 5-aminoimidazole4-carboxamide1-β-D-ribofuranoside (AICAR) treatment suppressed the cell differentiation induced by siRNA-ASNS. RNA-Seq identified 1,968 differentially expressed genes (DEGs) during chicken SMSC differentiation when overexpression ASNS. Gene ontology (GO) enrichment analysis revealed that these DEGs primarily participated in 8 biological processes, 8 cellular components, and 4 molecular functions. Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis identified several significantly enriched signaling pathways, such as the JAK-STAT signaling pathway, tumor necrosis factor signaling pathway, toll-like receptor signaling pathway, and PI3K-Akt signaling pathway.ConclusionASNS promotes proliferation while inhibits the differentiation of chicken SMSCs. This study provides a theoretical basis for studying the role of ASNS in muscle development.

Dataset Information

NRF2 Regulates Viability, Proliferation, Resistance to Oxidative Stress, and Differentiation of Murine Myoblasts and Muscle Satellite Cells.

Publications

NRF2 Regulates Viability, Proliferation, Resistance to Oxidative Stress, and Differentiation of Murine Myoblasts and Muscle Satellite Cells.

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