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Terminal differentiation of keratinocytes was damaged in type 2 diabetic mice

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Abstract

Aims

Although skin manifestations are common in diabetic patients, its characteristics are poorly identified. This study explored the differentiation process of keratinocytes in type 2 diabetes mellitus (T2DM) in vivo.

Methods

Back skin of T2DM model KKAy/TaJcl mice (KKAy) and C57BL/6JJcl mice (control) aged 8 and 12 weeks was used. The mRNA expression of differentiation markers of keratinocytes was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The expression of each marker in situ was examined immunohistochemically.

Results

KKAy mice showed hyperglycemia versus control mice. The histological findings showed increased thickness and structural impairment of epidermal tissue in KKAy mice. The qRT-PCR revealed that the expression of integrin beta 1 and keratin 14 in KKAy and control mice was identical. However, the expression of involucrin at 8 weeks, keratin 10 at 12 weeks, and filaggrin and loricrin at 8 and 12 weeks was decreased in KKAy mice. Immunohistochemical findings showed that filaggrin was markedly decreased in KKAy mice, though Ki-67 remained unchanged.

Conclusion

The terminal differentiation process was impaired in the diabetic skin, while keratinocyte proliferation was preserved. Damaged terminal differentiation of keratinocytes may contribute to impairment of the skin barrier function in diabetic dermatoses.

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Acknowledgements

We give special thanks to Sayaka Nomura for excellent technical assistance. This study was supported by grants-in-aid from Fujita Health University.

Funding

This study was supported by grants-in-aid from Fujita Health University to AS.

Author information

Authors and Affiliations

  1. Department of Endocrinology, Diabetes and Metabolism, Fujita Health University, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi, 470-1192, Japan

    Takeshi Takayanagi, Hiroyuki Hirai, Yohei Asada, Eisuke Tomatsu, Yoshiteru Maeda, Yasumasa Yoshino, Izumi Hiratsuka, Sahoko Sekiguchi-Ueda, Megumi Shibata, Yusuke Seino, Yoshihisa Sugimura, Mitsuyasu Itoh & Atsushi Suzuki

  2. Research Laboratories, Nippon Menard Cosmetic Co., Ltd, Nagoya, Aichi, Japan

    Takaaki Yamada & Seiji Hasegawa

  3. Department of Applied Cell and Regenerative Medicine, Fujita Health University, Toyoake, Aichi, Japan

    Hirohiko Akamatsu

Authors
  1. Takeshi Takayanagi
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  2. Hiroyuki Hirai
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Corresponding author

Correspondence to Atsushi Suzuki.

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Conflict of interest

TY and SH are employees of Nippon Menard Cosmetics Co., Ltd. Other authors do not have any financial or non-financial conflict of interest.

Ethical approval

The mice were handled ethically according to the Regulations for the Management of Laboratory Animals at Fujita Health University. The experimental protocol for the ethical use of these animals was approved by the Animal Care and Use Committee at Fujita Health University (Permit No.: M0271).

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All the authors have made a significant contribution to this manuscript, have seen and approved the final manuscript.

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Takayanagi, T., Hirai, H., Asada, Y. et al. Terminal differentiation of keratinocytes was damaged in type 2 diabetic mice. Mol Biol Rep 49, 5875–5882 (2022). https://doi.org/10.1007/s11033-022-07367-4

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