A hypothetical mechanism of intraepidermal neurite formation in NC/Nga mice with atopic dermatitis.
BACKGROUND
Pruritus is a symptom in atopic dermatitis (AD). Previous studies have reported that increased intraepidermal neurites are observed in AD, suggesting that the neuritogenesis is related to itching in the skin.


OBJECTIVE
This study was conducted to reveal the mechanism of intraepidermal neurite formation in AD.


METHODS
In this study, we used conventional (Conv) NC/Nga mice with AD. NC/Nga mice maintained in specific pathogen-free (SPF) condition were used as a control with no AD. Distribution of intraepidermal neurites and expression patterns of growth factors (NGF and amphiregulin (AR)) and cell-cell junctional molecules (E-cadherin, zona occludens 1 (ZO-1) and desmoglein 3 (Dsg3)) were examined in the skins by immunohistochemistry or quantitative RT-PCR. Furthermore, detection of gelatinase activity was performed with in situ zymography. The same experiments were conducted in ICR mice for comparison with NC/Nga mice.


RESULTS
Neurite density and expression levels of growth factors and gelatinase were remarkably increased in the epidermis of Conv-NC/Nga mice compared with those of SPF-NC/Nga mice. Decreased expression of E-cadherin and ZO-1 and misexpression of Dsg3 were also observed in the atopic skins. In comparison with ICR mice, increases of neurite density and gelatinase activity were found in the skins of SPF-NC/Nga mice but expression levels of growth factors and cell-cell junctional molecules were unchanged.


CONCLUSIONS
Increases of growth factors and gelatinase activity may be related to neurite outgrowth in the epidermis of atopic NC/Nga mice. Additionally, abnormal expressions of cell-cell junctional molecules in the epidermis may provide intercellular spaces for the neurite formation.
Tominaga
Mitsutoshi
M
Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan.
Ozawa
Sumiko
S
Ogawa
Hideoki
H
Takamori
Kenji
K
D066258:Amphiregulin; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D003876:Dermatitis, Atopic / Q000378:metabolism / Q000473:pathology*; D066255:EGF Family of Proteins; D004817:Epidermis / Q000294:innervation* / Q000378:metabolism / Q000473:pathology*; D018093:Gelatinases / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D007365:Intercellular Junctions / Q000473:pathology / Q000648:ultrastructure; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D008815:Mice, Inbred Strains; D008962:Models, Theoretical; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D016501:Neurites / Q000473:pathology* / Q000502:physiology; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D062826:Zonula Occludens-1 Protein
D066258:Amphiregulin; C587849:Areg protein, mouse; D015820:Cadherins; D066255:EGF Family of Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; D020932:Nerve Growth Factor; D018093:Gelatinases