ArticleAmerican journal of physiology. Cell physiology2011
Estrogen-related receptor α regulates skeletal myocyte differentiation via modulation of the ERK MAP kinase pathway.
Article in American journal of physiology. Cell physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 56 citations in OpenAlex.
- Estrogen-Related Receptor Alpha Promotes Skeletal Muscle Regeneration and Mitigates Muscular Dystrophy.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- 25-Hydroxycholesterol as a negative regulator of diaphragm muscle contractions via estrogen receptor and CaHistochemistry and cell biology · 2025Article
- Targeting ERRs to counteract age-related muscle atrophy associated with physical inactivity: a pilot study.Frontiers in physiology · 2025Article
- ERRα: unraveling its role as a key player in cell migration.Oncogene · 2024Review
- Nuclear receptors as potential therapeutic targets in peripheral arterial disease and related myopathy.The FEBS journal · 2023Review
- Estrogen-related Receptor Signaling in Skeletal Muscle Fitness.International journal of sports medicine · 2023Article
- Roles of Estrogen, Estrogen Receptors, and Estrogen-Related Receptors in Skeletal Muscle: Regulation of Mitochondrial Function.International journal of molecular sciences · 2023Review
- Estrogen-related receptor alpha is an AMPK-regulated factor that promotes ischemic muscle revascularization and recovery in diet-induced obese mice.FASEB bioAdvances · 2022Article
- The Effects of Maternal Intake of EPA and DHA Enriched Diet During Pregnancy and Lactation on Offspring's Muscle Development and Energy Homeostasis.Frontiers in physiology · 2022Article
- DUSP1 promotes muscle atrophy by inhibiting myocyte differentiation in cachectic patients.Frontiers in oncology · 2022Article
- Estrogen-related receptor α is involved in angiogenesis and skeletal muscle revascularization in hindlimb ischemia.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Regulation of the expression of the estrogen related receptors (ERRs).Cellular and molecular life sciences : CMLS · 2020Review
- Divergent Regulation of Myotube Formation and Gene Expression by E2 and EPA during In-Vitro Differentiation of C2C12 Myoblasts.International journal of molecular sciences · 2020Article
- The Signaling Pathways Project, an integrated 'omics knowledgebase for mammalian cellular signaling pathways.Scientific data · 2019Article
- Estrogen-Related Receptor γ Induces Angiogenesis and Extracellular Matrix Degradation of Temporomandibular Joint Osteoarthritis in Rats.Frontiers in pharmacology · 2019Article
- Establishment of stably expandable induced myogenic stem cells by four transcription factors.Cell death & disease · 2018Article
- ERRα suppression enhances the cytotoxicity of the MEK inhibitor trametinib against colon cancer cells.Journal of experimental & clinical cancer research : CR · 2018Article
- Loss of tafazzin results in decreased myoblast differentiation in C2C12 cells: A myoblast model of Barth syndrome and cardiolipin deficiency.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2018Article
- Reduced prostaglandin IFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Estrogen/ERR-α signaling axis is associated with fiber-type conversion of upper airway muscles in patients with obstructive sleep apnea hypopnea syndrome.Scientific reports · 2016Article
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2 authors at 1 institution in 1 country.
Funding
Abstract
Myocyte differentiation involves complex interactions between signal transduction pathways and transcription factors. The estrogen-related receptors (ERRs) regulate energy substrate uptake, mitochondrial respiration, and biogenesis and may target structural gene programs in striated muscle. However, ERRα's role in regulating myocyte differentiation is not known. ERRα and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) are coordinately upregulated with metabolic and skeletal muscle-specific genes early in myogenesis. We analyzed effects of ERRα overexpression and loss of function in myogenic models. In C2C12 myocytes ERRα overexpression accelerated differentiation, whereas XCT790 treatment delayed myogenesis and resulted in myotubes with fewer mitochondria and disorganized sarcomeres. ERRα-/- primary myocytes showed delayed myogenesis, resulting in structurally immature myotubes with reduced sarcomeric assembly and mitochondrial function. However, sarcomeric and metabolic gene expression was unaffected or upregulated in ERRα-/- cells. Instead, ERRα-/- myocytes exhibited aberrant ERK activation early in myogenesis, consistent with delayed myotube formation. XCT790 treatment also increased ERK phosphorylation in C2C12, whereas ERRα overexpression decreased early ERK activation, consistent with the opposing effects of these treatments on differentiation. The transient induction of MAP kinase phosphatase-1 (MKP-1), which mediates ERK dephosphorylation at the onset of myogenesis, was lost in ERRα-/- myocytes and in XCT790-treated C2C12. The ERRα-PGC-1α complex activates the Dusp1 gene, which encodes MKP-1, and ERRα occupies the proximal 5' regulatory region during early differentiation in C2C12 myocytes. Finally, treatment of ERRα-/- myocytes with MEK inhibitors rescued normal ERK signaling and myogenesis. Collectively, these data demonstrate that ERRα is required for normal skeletal myocyte differentiation via modulation of MAP kinase signaling.
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