STAT3 maintains skin barrier integrity by modulating SPINK5 and KLK5 expression in keratinocytes

Jaehyung Kim, Min Gyu Kim, Sang Hoon Jeong, Hee Joo Kim, Sang Wook Son

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


Skin barrier dysfunction induces skin inflammation. Signal transducer and activator of transcription 3 (STAT3) is known to be involved in Th17-mediated immune responses and barrier integrity in the cornea and intestine; however, its role in the skin barrier remains largely unknown. In this study, we elucidated the potential role of STAT3 in the skin barrier and its effect on kallikrein-related peptidase 5 (KLK5) and serine protease inhibitor Kazal-type 5 (SPINK5) expression using a mouse model with keratinocyte-specific ablation of STAT3. Keratinocyte-specific loss of STAT3 induced a cutaneous inflammatory phenotype with pruritus and intense scratching behaviour in mice. Transcriptomic analysis revealed that the genes associated with impaired skin barrier function, including KLK5, were upregulated. The effect of STAT3 on KLK5 expression in keratinocytes was not only substantiated by the increase in KLK5 expression following treatment with STAT3 siRNA but also by its decreased expression following STAT3 overexpression. Overexpression and IL-17A–mediated stimulation of STAT3 increased the expression of SPINK5, which was blocked by STAT3 siRNA. These results suggest that the expression of SPINK5 and KLK5 in keratinocytes could be dependent on STAT3 and that STAT3 might play an essential role in the maintenance of skin barrier homeostasis.

Original languageEnglish
Pages (from-to)223-232
Number of pages10
JournalExperimental Dermatology
Issue number2
Publication statusPublished - 2022 Feb

Bibliographical note

Funding Information:
This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) and funded by the Ministry of Science, ICT and Future Planning (NRF‐2019R1A2B5B01070162). Additionally, this work was supported by a Korea University grant. The funding sources had no involvement in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.

Publisher Copyright:
© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


  • KLK5
  • SPINK5
  • STAT3
  • homeostasis
  • skin barrier

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology


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