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Age-related decrease in muscle satellite cells is accompanied with diminished expression of early growth response 3 in mice

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Abstract

Skeletal muscle regeneration is mostly dependent on muscle satellite cells. Proper muscle regeneration requires enough number of satellite cells. Recent studies have suggested that the number of satellite cells in skeletal muscle declines as we age, leading to the impairment of muscle regeneration in older population. Our earlier study demonstrated that zinc finger transcription factor early growth response 3 (Egr3) plays an important role for maintaining the number of myoblasts, suggesting that age-related decrease in muscle satellite cell should be associated with the expression levels of Egr3. The aim of this study was to investigate whether aging would alter the Egr3 expression in satellite cells. A couple groups of male C57BL/6J mice were examined in this study: young (3 Mo) and old (17 Mo). Immunohistochemical staining showed that the satellite cell number decreased in normal and injured muscles of old mice. In fluorescence-activated cell sorting-isolated muscle satellite cells from normal and injured muscles, the mRNA expression of Egr3 was significantly decreased with age regardless of injury. In harmony with these results, Pax7 mRNA levels also decreased in the satellite cells from old mice. Alternatively, inhibition of Egr3 expression by shRNA decreased Pax7 protein expression in cultured myoblasts. These results suggest that Egr3 is associated with the age-related decline of muscle satellite cells in older population. Also, Egr3 might be implicated in the regulation of Pax7. Therefore, the loss of Egr3 expression may elucidate attenuated MSCs function and muscle regeneration in older age.

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Acknowledgements

Ms. Chiaki Kakehashi is acknowledged for animal maintenance. We thank Dr. James Clemons for his proofreading and statistical consultation of this manuscript. This work was partially supported by a research grant from the General Insurance Association of Japan to Y.O., by the Public Health Research Foundation to Y.O. and by JSPS KAKENHI Grants Number 18K10835 to Y.O., 15K01633 to M.K., 15K01632 to H.F.

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Authors and Affiliations

  1. Department of Physiology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan

    Yuji Ogura, Mitsutoshi Kurosaka & Toshiya Funabashi

  2. School of Kinesiology, University of Louisiana at Lafayette, Lafayette, LA, USA

    Shuichi Sato

  3. New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA, USA

    Shuichi Sato

  4. Department of Orthopaedic Surgery, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan

    Takashi Kotani

  5. Department of Sports Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan

    Hiroto Fujiya

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  1. Yuji Ogura
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Ogura, Y., Sato, S., Kurosaka, M. et al. Age-related decrease in muscle satellite cells is accompanied with diminished expression of early growth response 3 in mice. Mol Biol Rep 47, 977–986 (2020). https://doi.org/10.1007/s11033-019-05189-5

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