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.
|Journal||Allergy: European Journal of Allergy and Clinical Immunology|
|Publication status||Accepted/In press - 2022|
Bibliographical noteFunding Information:
This study was supported by Korea Mouse Phenotyping Project NRF‐2016M3A9D5A01952416 National Research Foundation (NRF) grant funded by the Korean Government (Ministry of Science, ICT and Future Planning) (KTN), NRF of Korea grant 2022R1A2C3007850 (KTN), The Korea Health Technology R&D project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (grant no. HP20C0061) (KTN), Brain Korea 21 PLUS Project for Medical Science at Yonsei University (KTN, COP), NRF of Korea grant 2021R1A2C2013347 (KML), NRF of Korea grant 2020R1A2C1009916 (COP), NRF of Korea grant 2022R1C1C2009361 (HJ).
© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy