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The significant role of autophagy in the granular layer in normal skin differentiation and hair growth

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Abstract

As a major intracellular degradation system, autophagy contributes to the maintenance of skin keratinocyte homeostasis. However, the precise role of autophagy in skin differentiation has not been fully investigated. To clarify whether autophagy plays a role in skin differentiation and maturation, autophagy-related gene 7 (Atg7)-deficient mice were generated. Atg7-deficient mice cannot survive for more than 24 h after birth. Therefore, the skins of Atg7-deficient mice and wild-type mice (as a control) were grafted onto severe combined immunodeficient mice. The resulting morphological and pathological changes were monitored for 28 days. Histopathological examination revealed acanthosis, hyperkeratosis, and abnormal hair growth in the skin grafts from the Atg7-deficient mice. Immune-density analysis of the skin grafts revealed reduced immunostaining of keratinization-related proteins, including loricrin, filaggrin, and involucrin, in the skin grafts from the Atg7-deficient mice. Furthermore, quantitative RT-PCR and Western blot analyses revealed the reduced expression of these three keratinization-related proteins in the skin grafts from the Atg7-deficient mice. Morphometric analysis using electron microscopy further revealed a reduction in the number and diameter of the keratohyalin and trichohyalin granules in these skin grafts. The differences were maintained for at least 1 month after transplantation. These results show that autophagy has a significant role in epidermal keratinization and hair growth until a certain stage of maturation.

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Acknowledgments

We are grateful to Dr. Norihito Tada, Dr. Takatoshi Kuhara, and the staff of the Atopy Research Center for breeding the Atg7-deficient mice. We thank Mr. Atsushi Furuhata and Ms. Yuko Kojima of the Laboratory of Biomedical Imaging Research, and Dr. Masato Koike and Mr. Mitsutaka Yoshida of the Laboratory of Ultrastructure Research and the Laboratory of Molecular and Biochemical Research, Research Support Center, Juntendo University Graduate School of Medicine, Tokyo, Japan, for technical assistance. This work was supported, in part, by the “Research on Measures for Intractable Diseases” Project matching fund subsidy (H23-028) from the Ministry of Health, Labor, and Welfare, Japan (AT, SI), a Grant-in-aid for Scientific Research on Priority Areas (18076005 to MK, TU), and a Research Grant from the Takeda Science Foundation (TU).

Conflict of interest

The authors declare that they have no conflicts of interest.

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Authors and Affiliations

  1. Department of Dermatology and Allergology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan

    Nagisa Yoshihara, Atsushi Takagi, Kunitaka Haruna, Yasushi Suga & Shigaku Ikeda

  2. Division of Proteomics and Biomolecular Science, Research Support Center, Juntendo University Graduate School of Medicine, Tokyo, Japan

    Takashi Ueno & Juan Alejandro Oliva Trejo

  3. Protein Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan

    Masaaki Komatsu & Keiji Tanaka

Authors
  1. Nagisa Yoshihara
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  2. Takashi Ueno
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  3. Atsushi Takagi
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  4. Juan Alejandro Oliva Trejo
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  5. Kunitaka Haruna
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  6. Yasushi Suga
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  7. Masaaki Komatsu
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  8. Keiji Tanaka
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  9. Shigaku Ikeda
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Correspondence to Shigaku Ikeda.

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Yoshihara, N., Ueno, T., Takagi, A. et al. The significant role of autophagy in the granular layer in normal skin differentiation and hair growth. Arch Dermatol Res 307, 159–169 (2015). https://doi.org/10.1007/s00403-014-1508-0

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  • DOI: https://doi.org/10.1007/s00403-014-1508-0

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