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Silencing of ERRα gene represses cell proliferation and induces apoptosis in human skin fibroblasts

  • Authors:
    • Naoki Nanashima
    • Toshio Norikura
    • Manabu Nakano
    • Chie Hata
    • Kayo Horie
  • View Affiliations / Copyright

    Affiliations: Department of Nutrition, Faculty of Health Science, Aomori University of Health and Welfare, Aomori 030‑8505, Japan, Department of Bioscience and Laboratory Medicine, Hirosaki University Graduate School of Health Sciences, Hirosaki, Aomori 036‑8564, Japan, Department of Biomedical Data Intelligence, Graduate School of Medicine, Kyoto University, Kyoto 606‑8397, Japan
    Copyright: © Nanashima et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 6
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    Published online on: October 18, 2024
       https://doi.org/10.3892/mmr.2024.13370
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Abstract

Estrogen‑related receptor (ERR) is an orphan nuclear receptor structurally akin to the estrogen receptor. ERR is expressed in tissues with active energy metabolism and regulates intracellular metabolic functions. Additionally, ERRs are known to be strongly expressed in the epidermis of skin tissue, but their functions are unknown. The present study investigated the function of ERRα in human skin fibroblasts. ERRα expressed in human dermal fibroblast TIG113 was knocked down using small interfering (si)RNA and gene expression was comprehensively analyzed using microarrays 48 h later. Pathway analysis was performed using Wikipathways on genes exhibiting expression changes of ≥1.5‑fold. Expression of cell cycle‑related and apoptosis‑related genes was compared using reverse transcription‑quantitative PCR. After treating TIG113 cells with siERRα for 72 h, cell proliferation was assessed using the Cell Counting Kit‑8 or a scratch wound healing assay and apoptotic cells were measured using the Poly Caspase Assay Kit. Cell cycle analysis was performed using flow cytometry. The expression of the ERRα gene was suppressed by siRNA. The expression of genes associated with cell cycle‑related pathways were decreased while that of those associated with apoptosis‑related pathways increased. Furthermore, the expression of cell cycle‑related genes such as cell division cycle 25C, cyclin E and cyclin B1 was decreased and the expression of apoptosis‑related genes such as caspase3 and Fas cell surface death receptor was increased. Cell proliferation was suppressed and the number of apoptotic cells increased ~2‑fold in ERRα‑knockdown TIG113 cells. Cell cycle analysis revealed that the number of cells in the Sub‑G1 phase increased and that in the S and G2/M phases decreased. The present study suggested that ERRα is an essential for the survival of human skin fibroblasts.
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Copy and paste a formatted citation
Spandidos Publications style
Nanashima N, Norikura T, Nakano M, Hata C and Horie K: Silencing of <em>ERR&alpha;</em> gene represses cell proliferation and induces apoptosis in human skin fibroblasts. Mol Med Rep 31: 6, 2025.
APA
Nanashima, N., Norikura, T., Nakano, M., Hata, C., & Horie, K. (2025). Silencing of <em>ERR&alpha;</em> gene represses cell proliferation and induces apoptosis in human skin fibroblasts. Molecular Medicine Reports, 31, 6. https://doi.org/10.3892/mmr.2024.13370
MLA
Nanashima, N., Norikura, T., Nakano, M., Hata, C., Horie, K."Silencing of <em>ERR&alpha;</em> gene represses cell proliferation and induces apoptosis in human skin fibroblasts". Molecular Medicine Reports 31.1 (2025): 6.
Chicago
Nanashima, N., Norikura, T., Nakano, M., Hata, C., Horie, K."Silencing of <em>ERR&alpha;</em> gene represses cell proliferation and induces apoptosis in human skin fibroblasts". Molecular Medicine Reports 31, no. 1 (2025): 6. https://doi.org/10.3892/mmr.2024.13370
Copy and paste a formatted citation
x
Spandidos Publications style
Nanashima N, Norikura T, Nakano M, Hata C and Horie K: Silencing of <em>ERR&alpha;</em> gene represses cell proliferation and induces apoptosis in human skin fibroblasts. Mol Med Rep 31: 6, 2025.
APA
Nanashima, N., Norikura, T., Nakano, M., Hata, C., & Horie, K. (2025). Silencing of <em>ERR&alpha;</em> gene represses cell proliferation and induces apoptosis in human skin fibroblasts. Molecular Medicine Reports, 31, 6. https://doi.org/10.3892/mmr.2024.13370
MLA
Nanashima, N., Norikura, T., Nakano, M., Hata, C., Horie, K."Silencing of <em>ERR&alpha;</em> gene represses cell proliferation and induces apoptosis in human skin fibroblasts". Molecular Medicine Reports 31.1 (2025): 6.
Chicago
Nanashima, N., Norikura, T., Nakano, M., Hata, C., Horie, K."Silencing of <em>ERR&alpha;</em> gene represses cell proliferation and induces apoptosis in human skin fibroblasts". Molecular Medicine Reports 31, no. 1 (2025): 6. https://doi.org/10.3892/mmr.2024.13370
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