Improvement of atopic dermatitis-like symptoms in a murine model via the chromogranin A-derived peptide catestatin.

Background: Atopic dermatitis (AD), a prevalent chronic inflammatory skin disorder, is characterized by compromised skin barrier and heightened immune responses. The study investigates the therapeutic efficacy of catestatin (CST), a chromogranin A-derived antimicrobial peptide, in mitigating AD-like symptoms.

Methods: Utilizing both keratinocyte cultures and a C57BL/6 mouse model, we examined CST's impact on skin barrier proteins, tight junction (TJ) integrity, inflammatory cytokines, and AD-like symptoms.

Results: CST administration led to a significant upregulation of skin barrier proteins and improved TJ function, counteracting the negative effects of Th2 cytokines on these parameters. In a 2,4-dinitrochlorobenzene-induced AD mouse model, CST treatment markedly reduced AD-like symptoms, including ear thickness, transepidermal water loss, and scratching behavior, and normalized barrier protein expression and TJ barrier function. Furthermore, CST was found to interact with the Notch1 receptor, activating the Notch1/PKC pathway, which may underlie its skin barrier-enhancing properties.

Conclusions: Collectively, these findings suggest CST as a promising therapeutic agent for AD, capable of enhancing skin barrier function, modulating immune responses, and targeting the Notch1/PKC pathway, offering a novel approach to AD treatment focusing on barrier restoration and immune modulation.