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Stratum corneum proteases and dry skin conditions

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Abstract

This paper reviews the role of stratum corneum (SC) proteases and their inhibitors in normal and xerotic skin conditions. The importance of the corneodesmosome for SC integrity is also discussed, and the effect of proteases on its disassembly. The relevance of each enzyme class is outlined, as well as their potential inhibitors. It is becoming much clearer, however, that the LEKTI family of inhibitors are critical for SC enzyme control. Delayed desquamation is the accumulation of corneocytes on the surface of the SC that leads ultimately to the cosmetic condition commonly termed as “dry skin”. The reductions of serine protease activity are a consistent theme in dry skin, and non-eczematous atopic dermatitis otherwise known as atopic xerosis leading to retention hyperkeratosis. Flaky skin is normally seen on the body whereas a rough skin is observed on the face. Increased protease activity occurs in most, if not all, inflammatory dermatoses, ranging from the genetic disorders, psoriasis and eczematous atopic dermatitis to sub-clinical barrier abnormalities induced by surfactants or by environmental influences as a result of premature desquamation. In some of these conditions a thinner SC is apparent, e.g., eczematous atopic skin or on photodamaged facial skin. A better understanding of the proteolytic events and of the regulatory mechanisms involved in desquamation should enable the design of new treatments for skin disorders associated with faulty desquamation. This new knowledge will be an important basis for new developments in ‘corneotherapy’ and ‘corneocare’.

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Abbreviations

A2ML1:

α2-macroglobulin-like-1

AD:

Atopic dermatitis

CE:

Cornified envelope

CDSN:

Corneodesmosin

CTSD:

Cathepsin D

CTSL2:

Cathepsin L2 = cathepsin V = stratum corneum thiol protease = SCTP

CTSL-like:

Cathepsin L-like

DSC:

Desmocollin

DSG:

Desmoglein

Elafin:

Skin-derived-antileukoprotease = SKALP

KLK:

Kallikrein

KLK5:

Stratum corneum trypsin-like enzyme = SCTE

KLK7:

Stratum corneum chymotrypsin-like enzyme = SCCE

LB:

Lamellar body (?)

LEKTI-1:

Lymphoepithelial Kazal-type 5 serine protease inhibitor

LEKTI-2:

Lymphoepithelial Kazal-type 9 serine protease inhibitor

LEKTI-3:

Lymphoepithelial Kazal-type 6 serine protease inhibitor

PAI-2:

Plasminogen activator inhibitor-2 = SERPINB2

SC:

Stratum corneum

SG:

Stratum granulosum

SLPI:

Secretory leukocyte protease inhibitor = antileukoprotease (ALP)

SPINK5:

Serine protease inhibitor Kazal-type 5 gene

SPINK6:

Serine protease inhibitor Kazal-type 6 gene

SPINK9:

Serine protease inhibitor Kazal-type 9 gene

TEWL:

Transepidermal water loss

TJ:

Tight junction

uPA:

Urokinase = urokinase type plasminogen activator

uPAR:

Urokinase-type plasminogen activator receptor

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  1. AVR Consulting Ltd., 26 Shavington Way, Kingsmead, Northwich, Cheshire, CW9 8FH, UK

    Anthony V. Rawlings

  2. DSM Nutritional Products Ltd., P.O. Box 2676, Bldg. 203-4/86, 4002, Basel, Switzerland

    Rainer Voegeli

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Rawlings, A.V., Voegeli, R. Stratum corneum proteases and dry skin conditions. Cell Tissue Res 351, 217–235 (2013). https://doi.org/10.1007/s00441-012-1501-x

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