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Updated: May 30, 2026

Cultivating a Three-dimensional Reconstructed Human Epidermis at a Large Scale
Published on: May 28, 2021
Expression of epidermal CAMP changes in parallel with permeability barrier status
Marina Rodriguez-Martin1, Gemma Martin-Ezquerra, Mao-Qiang Man
1Dermatology Service, Hospital Universitario de Canarias, University of La Laguna, Tenerife, Spain.
Abstract:
Two critical defensive functions of the outer epidermis, the permeability barrier and antimicrobial defense, share certain structural and biochemical features. Moreover, three antimicrobial peptides (AMPs), i.e., mouse β-defensin 3 (mBD3), mouse cathelicidin antimicrobial peptide (mCAMP), and the neuroendocrine peptide, catestatin (Cst), all localize to the outer epidermis, and both mBD3 and mCAMP are secreted from the epidermal lamellar bodies with other organelle contents that subserve the permeability barrier. These three AMPs are upregulated in response to acute permeability barrier disruption, whereas conversely, mCAMP-/- mice (unable to combat Gram-positive pathogens) also display abnormal barrier homeostasis. To determine further whether these two functions are co-regulated, we investigated changes in immunostaining for these three AMPs in skin samples in which the permeability barrier function in mice had been either compromised or enhanced. Compromised or enhanced barrier function correlated with reduced or enhanced immunohistochemical expression of mCAMP, respectively, but conversely with Cst expression, likely due to the role of this AMP as an endogenous inhibitor of cathelicidin expression. mBD3 expression correlated with experimental barrier perturbations, but poorly with developmental changes in barrier function. These studies show that changes in cathelicidin and Cst expression parallel changes in permeability barrier status, with a less clear relationship with mBD3 expression.
Insights
The outer epidermis
Area of Science:
- Dermatology
- Immunology
- Biochemistry
Background:
- The skin's outer epidermis has two key defenses: a permeability barrier and antimicrobial defense.
- These functions share structural and biochemical traits, with antimicrobial peptides (AMPs) like mouse β-defensin 3 (mBD3), mouse cathelicidin antimicrobial peptide (mCAMP), and catestatin (Cst) found in the epidermis.
- mBD3 and mCAMP are released from epidermal lamellar bodies, contributing to barrier function.
Purpose of the Study:
- To investigate the co-regulation of epidermal permeability barrier and antimicrobial defense functions.
- To examine how alterations in barrier status affect the expression of mBD3, mCAMP, and Cst in mouse skin.
Main Methods:
- Immunohistochemical analysis of mouse skin samples with compromised or enhanced permeability barrier function.
- Assessment of mBD3, mCAMP, and Cst expression levels in relation to barrier status.
Main Results:
- Mouse cathelicidin antimicrobial peptide (mCAMP) expression positively correlated with barrier function, while catestatin (Cst) expression showed an inverse correlation.
- Mouse β-defensin 3 (mBD3) expression correlated with experimental barrier disruptions but not developmental changes.
- These findings suggest co-regulation between barrier homeostasis and specific antimicrobial peptides.
Conclusions:
- Cathelicidin and catestatin expression levels dynamically parallel changes in skin barrier status.
- The relationship between mBD3 expression and barrier function is less direct.
- These AMPs play a role in maintaining skin barrier integrity and defense.
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