Terminal differentiation of keratinocytes was damaged in type 2 diabetic mice

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

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)5875-5882
Number of pages8
JournalMolecular Biology Reports
Issue number7
Publication statusPublished - 07-2022

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics


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