Repetin Regulates Epidermal Barrier Homeostasis and Is Associated With Inflammatory Skin Diseases

Area of Science:

• Dermatology
• Molecular Biology
• Biochemistry

Background:

• Repetin (RPTN) is an S100 protein family member implicated as a susceptibility gene for atopic dermatitis (AD).
• The precise biological functions of RPTN in skin homeostasis and disease remain largely unelucidated.
• Understanding RPTN's role is vital for addressing inflammatory skin conditions like AD.

Purpose of the Study:

• To investigate the role of Repetin (RPTN) in maintaining epidermal homeostasis.
• To explore the involvement of RPTN in inflammatory skin diseases.
• To determine the regulation of RPTN expression by cytokines in skin models.

Main Methods:

• Examined RPTN expression in normal skin, inflammatory skin diseases, and differentiated normal human keratinocytes (NHKs).
• Performed functional analyses using RPTN knockdown (KD) NHKs and 3D skin-equivalent models.
• Assessed epidermal barrier function via lucifer yellow permeability assay and evaluated cytokine-mediated RPTN regulation in 3D AD and psoriasis models.

Main Results:

• RPTN expression increased with keratinocyte differentiation, primarily in the granular layer of normal epidermis.
• RPTN deficiency in 3D models impaired epidermal barrier function and upregulated differentiation genes (e.g., FLG, IVL, TGM1).
• RPTN knockdown increased IL-25 expression; RPTN was elevated in AD lesions and other hypergranular skin conditions, with IL-4 and IL-13 inducing RPTN in a 3D AD model.

Conclusions:

• Repetin (RPTN) plays a significant role in maintaining epidermal barrier homeostasis.
• RPTN expression is altered in various inflammatory skin diseases, including atopic dermatitis.
• RPTN may be involved in regulating inflammatory responses and keratinocyte differentiation in the skin.