The Suppressive Effect of Leucine-Rich Glioma Inactivated 3 (LGI3) Peptide on Impaired Skin Barrier Function in a Murine Model Atopic Dermatitis.

Ui Seok Kim,Ji Hoon Jeong,Dong-Seok Kim,A M Abd El-Aty,Tae Woo Jung,Jong Hyuk Lee,Eon Sub Park,Joon Seok Bang,Jin Woo Park

doi:10.3390/pharmaceutics12080750

Abstract

This study aimed to restore the skin barrier function from atopic dermatitis (AD) via treatment with leucine-rich glioma inactivated 3 (LGI3) peptide. Male NC/Nga mice (7 weeks, 20 g) were randomly allocated into three groups (control, AD, and LGI3 group). After induction of AD skin lesions with Dermatophagoides farinae ointment, mice were treated with LGI3. The clinical score of AD was the highest and the dorsal skin thickness was the thickest in the AD group. In contrast, LGI3 treatment improved the clinical score and the dorsal skin thickness compared to the AD model. LGI3 treatment suppressed histopathological thickness of the epithelial cell layer of the dorsal skin. LGI3 treatment could indirectly reduce mast cell infiltration through restoring the barrier function of the skin. Additionally, the filaggrin expression was increased in immunohistochemical evaluation. In conclusion, the ameliorating effect and maintaining skin barrier homeostasis in the AD murine model treated with LGI3 could be attributed to complete re-epithelialization of keratinocytes. Hence, LGI3 might be considered as a new potential therapeutic target for restoring skin barrier function in AD.

Highlights

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease, which affects at least 15% of children
The atopic dermatitis (AD) mouse model displayed a low level of leucine-rich glioma inactivated 3 (LGI3) peptide in serum and damaged skin barrier
This study hypothesized that suppression of LGI3 appears to be closely associated with impairment of skin barrier in AD, and treatment with LGI3 might be crucial to restore the damaged skin barrier in AD

Summary

Introduction

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease, which affects at least 15% of children. The disease is caused by a complex interaction between genetic, skin, immune, and environmental factors [1,2,3,4,5]. AD skin appears frequently dry and shows severe itching when coming into direct contact with an irritant compared to healthy skin. The disease is classified into two categories based on clinical features: acute and chronic AD. In acute AD, the symptoms are severe pruritus, erythematous papules associated with excoriation and severe exudative lesions. Chronic AD skin lesions are associated with thickened plaques with wrinkled lichenification, increased collagen deposition in the dermis, and dry fibrotic papules [5]

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