Computational modelling predicts impaired barrier function and higher sensitivity to skin inflammation following pH
Eléa Thibault Greugny1,2, Jalil Bensaci1, François Fages2
1Essential Health Translational Science, Johnson & Johnson Santé Beauté France, Issy-les-Moulineaux, France.
Experimental Dermatology
|November 2, 2022
Summary
Elevated skin surface pH disrupts epidermal homeostasis by increasing serine protease activity, weakening the skin barrier and increasing inflammation. Targeting pH and proteases may improve skin barrier function.
Area of Science:
- Dermatology
- Computational Biology
- Biophysics
Background:
- Skin surface pH regulates epidermal homeostasis via serine protease activity.
- Kallikreins (KLK) degrade corneodesmosomes, a process inhibited by LEKTI.
- Increased skin surface pH is linked to impaired barrier function in conditions like atopic dermatitis.
Purpose of the Study:
- To model the impact of skin surface pH changes on epidermal properties.
- To investigate the role of the LEKTI-KLK mechanism in pH-mediated barrier function.
- To explore potential therapeutic targets for improving skin barrier integrity.
Main Methods:
- Development of an agent-based model of the epidermis.
- Simulation of altered skin surface pH conditions.
- Analysis of epidermal water loss, irritant permeation, and inflammation response.
Main Results:
- Less acidic skin surface pH significantly increases water loss and irritant permeation.
- Weakened skin barrier function leads to heightened inflammation upon irritant exposure.
- The LEKTI-KLK pathway is crucial in mediating pH-induced changes in skin barrier properties.
Conclusions:
- Skin surface pH is a critical factor in maintaining epidermal barrier integrity.
- Serine proteases, regulated by LEKTI, are key mediators of pH effects on the skin barrier.
- Modulating skin surface pH and serine protease activity presents a promising therapeutic strategy for skin barrier disorders.
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