机构：[1]Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Institute of Dermatology & Venereology of Yunnan Province, Kunming, China昆明医科大学附属第一医院内科科室皮肤科[2]Department of Dermatology, People’s Hospital of Henan Province, Zhengzhou, China[3]Department of Physiology, Kunming Medical University, Kunming, China[4]Dermatology Service, Veterans Affairs Medical Center, and Department of Dermatology, University of California, San Francisco, USA[5]Skin Health Research Center, Yunnan Characteristic Plant Extraction Laboratory, Kunming, China
BackgroundSensitive skin is hypersensitive to various external stimuli and a defective epidermal permeability barrier is an important clinical feature of sensitive skin. Claudin-5 (CLDN5) expression levels decrease in sensitive skin. This study aimed to explore the impact of CLDN5 deficiency on the permeability barrier in sensitive skin and the regulatory role of miRNAs in CLDN5 expression.Materials and methodsA total of 26 patients were retrospectively enrolled, and the CLDN5 expression and permeability barrier dysfunction in vitro were assessed. Then miRNA-224-5p expression was also assessed in sensitive skin.ResultsImmunofluorescence and electron microscopy revealed reduced CLDN5 expression, increased miR-224-5p expression, and disrupted intercellular junctions in sensitive skin. CLDN5 knockdown was associated with lower transepithelial electrical resistance (TEER) and Lucifer yellow penetration in keratinocytes and organotypic skin models. The RNA-seq and qRT-PCR results indicated elevated miR-224-5p expression in sensitive skin; MiR-224-5p directly interacted with the 3`UTR of CLDN5, resulting in CLDN5 deficiency in the luciferase reporter assay. Finally, miR-224-5p reduced TEER in keratinocyte cultures.ConclusionThese results suggest that the miR-224-5p-induced reduction in CLDN5 expression leads to impaired permeability barrier function, and that miR-224-5p could be a potential therapeutic target for sensitive skin.
基金：
National Natural Science Foundation of
Yunnan Province Clinical Center for Skin
Immune Diseases, Grant/Award Number:
ZX2019-03-02; Yunnan Province Clinical
Research Center for Skin Immune Diseases,
Grant/Award Number: 2019ZF012; Program
for Innovative Research Team in Ministry of
Education of China, Grant/Award Number:
IRT17-R49
第一作者机构：[1]Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Institute of Dermatology & Venereology of Yunnan Province, Kunming, China[2]Department of Dermatology, People’s Hospital of Henan Province, Zhengzhou, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Institute of Dermatology & Venereology of Yunnan Province, Kunming, China[5]Skin Health Research Center, Yunnan Characteristic Plant Extraction Laboratory, Kunming, China[*1]Department of Dermatology, First Affiliated Hospital of Kunming Medical University, and Institute of Dermatology & Venereology of Yunnan Province, 295 Xichang Road, Kunming 650032, China.
推荐引用方式(GB/T 7714)：
Yang Li,Wu Wen-Juan,Lyu Le-Chun,et al.MiRNA-224-5p regulates the defective permeability barrier in sensitive skin by targeting claudin-5[J].SKIN RESEARCH AND TECHNOLOGY.2024,30(5):doi:10.1111/srt.13720.
APA：
Yang, Li,Wu, Wen-Juan,Lyu, Le-Chun,Tu, Ying,Gu, Hua...&He, Li.(2024).MiRNA-224-5p regulates the defective permeability barrier in sensitive skin by targeting claudin-5.SKIN RESEARCH AND TECHNOLOGY,30,(5)
MLA：
Yang, Li,et al."MiRNA-224-5p regulates the defective permeability barrier in sensitive skin by targeting claudin-5".SKIN RESEARCH AND TECHNOLOGY 30..5(2024)
