RAB25 coordinates filaggrin-containing keratohyalin granule maturation and affects atopic dermatitis severity

Haengdueng Jeong, Nakyum Lee, Chanyang Uhm, Kyungrae Cho, Heeju Oh, Yeseul Oh, Ke Lun Zhang, Hye Li Kim, James R. Goldenring, Kyung Min Lim, Chang Ook Park, Ki Taek Nam

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Background: Keratohyalin granules (KHGs) supply the critical epidermal protein constituents such as filaggrin for maintaining skin barrier function during epidermal differentiation; however, their regulating mechanism remains largely unelucidated. Methods: To investigate the role of Ras-related protein Rab-25 (RAB25) expression in skin disease, we utilized skin specimens of patients with moderate-to-severe atopic dermatitis (AD) and healthy controls. To investigate the susceptibility of Rab25 knockout mice to AD, we established an oxazolone-induced AD model. Results: We investigated the role of RAB25 in KHG maturation and AD. RAB25-deficient mice showed a disrupted stratum corneum along with skin barrier dysfunction, decreased KHG production, and abnormal KHG processing. Consistently, in the human keratinocyte cell line HaCaT, RAB25 co-expressed with filaggrin-containing KHG and RAB25 silencing impaired KHG formation, which was attributable to abnormal actin dynamics. Most importantly, RAB25 expression was severely downregulated in the skin lesions of patients with AD, which was strongly correlated with disease severity scores. Conclusions: RAB25 coordinates KHG homeostasis by regulating actin dynamics and is critical for epidermal differentiation and the pathophysiology of AD.

Original languageEnglish
Pages (from-to)1007-1019
Number of pages13
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume78
Issue number4
DOIs
StatePublished - Apr 2023

Bibliographical note

Publisher Copyright:
© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.

Keywords

  • Filaggrin
  • Keratohyalin granule
  • RAB25
  • atopic dermatitis

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