Establishment of a mouse skin model of the lichenification in human chronic eczematous dermatitis.
BACKGROUND
Repeated mechanical stresses, such as scratching and rubbing, on a lesional skin area induce a rough skin condition known as lichenification in patients with chronic eczematous dermatitis. For ethical reasons, the pathomechanisms involved are difficult to study, so an animal model is required.


OBJECTIVE
To study the pathomechanisms of the unique rough skin changes seen in chronic eczematous dermatitis, we established a mouse skin model by repeated tape stripping to inflict stratum corneum (SC) barrier disruption. The skin characteristics of the model were investigated biologically, histologically and pharmacologically.


METHODS
Tape stripping was done on mouse back skin three times a week for 4 weeks. The skin changes were studied by obtaining negative replicas, haematoxylin and eosin staining, immunostaining for CD31 and BrdU, and measuring epidermal and cutaneous thickness and skin capacitance. Activities of matrix metalloproteinase (MMP)-2, 9 and urokinase-type plasminogen activator (uPA) in the skin tissues were analysed by zymography. The effects of MMP inhibitor and glycine were assessed.


RESULTS
The repeated tape stripping produced crusting and desquamation at 48 h, followed 1 week later by the formation of shallow furrows, which became much deeper after 4 weeks, appearing as fine and regular wrinkles. The resultant wrinkled skin resembled lichenified skin seen in patients with chronic eczematous dermatitis. Histopathologically, we found acanthosis, hypergranulosis and hyperkeratosis even at 48 h, and the skin was 2.5 times thicker than untreated control skin at 4 weeks. We observed angiogenesis in the upper dermis at 1 and 4 weeks. Skin capacitance, a parameter of SC hydration, displayed consistently low levels throughout the experimental period. Although the dermis was also thickened, the activity of MMP-9 was sharply increased only at 24 and 48 h after tape stripping, declining thereafter to the control level. Topical applications of CGS-27023A (CGS), an MMP inhibitor, failed to suppress this tape-stripping-induced wrinkle formation. In contrast, topical applications of a barrier recovery accelerator, glycine, effectively inhibited the wrinkle formation induced by repeated tape stripping.


CONCLUSIONS
The induction of fine and regular wrinkles by inflicting chronic SC barrier disruption in this model involves mainly epidermal changes, which is in sharp contrast to the mainly dermal changes induced by chronic ultraviolet B irradiation.
Matsunaga
Y
Y
Skin Biology Research Laboratories, Shiseido Life Science Research Center, 2-12-1 Fukuura, Yokohama, Japan. yukiko.matsunaga@to.shiseido.co.jp
Ogura
Y
Y
Ehama
R
R
Amano
S
S
Nishiyama
T
T
Tagami
H
H
D000818:Animals; D004195:Disease Models, Animal; D004485:Eczema / Q000473:pathology*; D004817:Epidermis / Q000187:drug effects / Q000473:pathology*; D005998:Glycine / Q000494:pharmacology; D018684:Glycine Agents / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008297:Male; D008666:Metalloendopeptidases / Q000494:pharmacology; D051379:Mice; D008812:Mice, Hairless; D011719:Pyrazines / Q000494:pharmacology; D015595:Skin Aging / Q000187:drug effects / Q000473:pathology; D013449:Sulfonamides / Q000494:pharmacology
C097658:CGS 27023A; D018684:Glycine Agents; D006877:Hydroxamic Acids; D011719:Pyrazines; D013449:Sulfonamides; D008666:Metalloendopeptidases; D005998:Glycine