NRF2 Regulates Viability, Proliferation, Resistance to Oxidative Stress, and Differentiation of Murine Myoblasts and Muscle Satellite Cells.
Iwona Bronisz-BudzyńskaMagdalena KozakowskaKatarzyna Pietraszek-GremplewiczMagdalena MadejAlicja JózkowiczAgnieszka LobodaJozef DulakPublished in: Cells (2022)
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.
Keyphrases
- oxidative stress
- induced apoptosis
- skeletal muscle
- transcription factor
- cell cycle arrest
- wild type
- endoplasmic reticulum stress
- mesenchymal stem cells
- diabetic rats
- dna damage
- type diabetes
- cell death
- risk factors
- cell proliferation
- umbilical cord
- metabolic syndrome
- endothelial cells
- binding protein
- cell therapy
- pi k akt
- anti inflammatory