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RAB25 coordinates filaggrin-containing keratohyalin granule maturation and affects atopic dermatitis severity.
Jeong, Haengdueng; Lee, Nakyum; Uhm, Chanyang; Cho, Kyungrae; Oh, Heeju; Oh, Yeseul; Zhang, KeLun; Kim, Hye Li; Goldenring, James R; Lim, Kyung-Min; Park, Chang Ook; Nam, Ki Taek.
Afiliação
  • Jeong H; Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
  • Lee N; Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
  • Uhm C; Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
  • Cho K; Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
  • Oh H; Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
  • Oh Y; Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
  • Zhang K; Department of Dermatology, Cutaneous Biology Research Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
  • Kim HL; Department of Dermatology, Cutaneous Biology Research Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
  • Goldenring JR; Epithelial Biology Center, Nashville VA Medical Center, Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
  • Lim KM; College of Pharmacy, Ewha Womans University, Seoul, South Korea.
  • Park CO; Department of Dermatology, Cutaneous Biology Research Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
  • Nam KT; Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
Allergy ; 78(4): 1007-1019, 2023 04.
Article em En | MEDLINE | ID: mdl-36383036
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Dermatite Atópica Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Dermatite Atópica Idioma: En Ano de publicação: 2023 Tipo de documento: Article