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The epidermal barrier function is dependent on the serine protease CAP1/Prss8.
Céline Leyvraz1, Roch-Philippe Charles, Isabelle Rubera
1Département de Pharmacologie et de Toxicologie, Université de Lausanne, CH-1005 Lausanne, Switzerland.
The Journal of Cell Biology
|August 3, 2005
Summary
Mice lacking channel-activating serine protease 1 (CAP1/Prss8) in skin died shortly after birth due to severe skin barrier defects. This protease is essential for epidermal development and postnatal survival.
Area of Science:
- Biochemistry
- Dermatology
- Developmental Biology
Background:
- Serine proteases regulate physiological processes.
- Channel-activating serine protease 1 (CAP1/Prss8), also known as prostasin, is a serine protease.
Purpose of the Study:
- To investigate the role of CAP1/Prss8 in epidermal development and skin barrier function.
- To determine the necessity of CAP1/Prss8 for postnatal survival.
Main Methods:
- Generation of CAP1/Prss8-deficient mice.
- Assessment of skin barrier function using dehydration, permeability assays, and transepidermal water loss measurements.
- Analysis of epidermal differentiation markers, SC lipid composition, corneocyte morphogenesis, and tight junction proteins.
Main Results:
- CAP1/Prss8-deficient mice exhibited embryonic lethality within 60 hours of birth, with lower body weight and severe stratum corneum malformation.
- Impaired skin barrier function was evidenced by dehydration and increased permeability, leading to fatal dehydration.
- Despite no major alterations in differentiation markers, CAP1/Prss8 deficiency disturbed SC lipid composition, corneocyte morphogenesis, and profilaggrin processing.
- Absence of occludin was observed, but this did not impede tracer diffusion.
Conclusions:
- Epidermal CAP1/Prss8 expression is critical for establishing a functional epidermal permeability barrier.
- CAP1/Prss8 is indispensable for postnatal survival, highlighting its vital role in skin development.