Scleroderma-like remodeling induced by type V collagen.
Recently, we discovered that New Zealand rabbits immunized with human type V collagen plus Freund's adjuvant present fibrosis and vasculitis of organs usually affected by systemic sclerosis. In this way, we studied the fibrillogenesis process to identify possible factors involved in altered remodeling observed in this scleroderma-like model. Additionally, we have done a very preliminary comparison with human skins obtained from scleroderma patients (n=3). Female New Zealand rabbits (n=10) were immunized subcutaneously with two doses of 1 mg collagen V (COL V) plus complete Freund's adjuvant for a 30-day interval, followed by two additional intramuscular booster immunizations in incomplete Freund's adjuvant for a 15-day interval. Animals from control group (n=10), were only inoculated with complete and incomplete Freund's adjuvant given at same conditions of COL V. Histological analysis of skins from animals and patients were done by Masson's trichrome staining, and immunofluorescence method to detect collagen fibers and interactions of types I, III and V collagen in the remodeling process. The analysis of animal skins showed collagen fibril deposits in the dermis after 7 days of sensibilization and an increase in these deposits after 75 and 120 days, respectively. Skin thickness and atrophy of sebaceous and sweat glands were progressively more intense in late sacrificed animals and correlated with increased amount of collagen deposition. Surprisingly, type V collagen was overexpressed both in animals and patients, forming dense and atypical collagen fibers in the dermis. We suggest that this anomalous expression of morphologically different type V collagen could justify the remodeling observed in scleroderma plaque.
Bezerra
Mailze Campos
MC
Discipline of Rheumatology, University of São Paulo, São Paulo, Brazil.
Teodoro
Walcy Rosolia
WR
de Oliveira
Cristiane Carla
CC
Velosa
Ana Paula Pereira
AP
Ogido
Luciana Tsuzuki Ichicawa
LT
Gauditano
Giancarla
G
Parra
Edwin Roger
ER
Capelozzi
Vera Luiza
VL
Yoshinari
Natalino Hajime
NH
D000328:Adult; D000818:Animals; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D024062:Collagen Type V / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007114:Immunization; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011817:Rabbits; D012595:Scleroderma, Systemic / Q000209:etiology / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D024042:Collagen Type I; D024061:Collagen Type III; D024062:Collagen Type V