DYNAMIC COLLAGEN V REMODELING IS RELATED TO SKIN THICKENING IN SSc
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conferenceObject
Data de publicação
2012
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OXFORD UNIV PRESS
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Citação
RHEUMATOLOGY, v.51, suppl.2, p.15-15, 2012
Resumo
Background. Normal physiological properties of skin, one of the primary organs affected in SSc, depends on collagen Types I (COL I), III (COLIII) and V (COLV) assembly forming heterotypic fibres. COLV regulates fibril diameter and loss of this function could result in tissue fibrosis. In this way, our aim was to evaluate the histological and molecular profiles of COLI, COLIII and COLV in SSc skin and its correlation with skin thickening and disease activity. Methods. Skin biopsies of 18 patients (5 at early and 13 at late disease stage) and 10 healthy controls were studied. Assessment of skin thickening was performed using the modified Rodnan skin score (MRSS) and disease activity was calculated by Valentini Disease Activity Index. Quantification of COLI, COLIII and COLV was evaluated by histomorphometry in dermis and quantitative RT–PCR in dermal fibroblast culture. Results. A higher expression of abnormal COLV was observed in dermis of patients with early disease when compared with control group and late disease. The COLIII content was also higher in early SSc when compared with healthy controls and late SSc. On the other hand, the amount of COLI was higher in late disease when compared with control and early SSc. A positive correlation between COLV and MRSS (r = 0.42, P = 0.04) as well as disease activity (r = 0.45, P = 0.03) was observed, but there was no correlation between COLI and COLIII expression and these parameters. COLV α-1 and COLV α-2, as well as COLI α-1 and COLIII α-1 mRNA expression were higher in SSc when compared with control group. Conclusion. We found increased COLIII and COLV deposition in early SSc and increased COLI expression in late SSc indicating that collagen remodelling in SSc is a dynamic process. The fact that abnormal COLV expression decreases in later disease stages could explain why skin thickening sometimes improves spontaneously with time. Besides, COLV is correlated to MRSS and disease activity. These findings include COLV as an important regulator of cutaneous thickness in SSc and may add this protein as a new target for future treatments.