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conferenceObject DYNAMIC COLLAGEN V REMODELING IS RELATED TO SKIN THICKENING IN SSc(2012) MARTIN, P.; TEODORO, W. R.; VELOSA, A. P.; CARRASCO, S.; MORAIS, J. de; CHRISTMANN, R. B.; PARRAS, E. R.; CAPELOZZI, V. L.; YOSHINARI, N. H.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.conferenceObject TRIDIMENSIONAL RECONSTRUCTION, BIOCHEMICAL AND MOLECULAR PROFILE OF COLLAGEN V IN SKIN AND LUNG FIBROBLASTS CULTURE FROM SSc INDICATE A FAILING IN FIBRILOGENESIS(2012) TEODORO, W.; MORAIS, J.; MARTIN, P.; VELOSA, A. P. P.; CARRASCO, S.; SOUZA, R. B. C.; KATAYAMA, M. L.; GOLDEINSTEIN-SCHAINBERG, C.; PARRA, E. R.; CAPELOZZI, V. L.; YOSHINARI, N. H.Background. The type V collagen (COL V) mutations are involved in collagen vascular diseases, such as SSc, in which an unusual accumulation of this collagen was demonstrated (Pathol Res Pract 2004; 200:681). In this context, our purpose was to analyse the 3D reconstruction, biochemical and molecular profile of COL Vα1 and α2 chains in skin and lung fibroblasts culture from patients with SSc. Methods. Lung biopsies of seven patients, skin of six patients and respective matched controls were obtained from SSc according ACR. For fibroblast culture skin and lung evaluations were used the following score: intense expression (1–4), fibroblast number/field (1, 2) and collagen fibres architecture (1–3). The total evaluations were: mild (3–5), moderate (6, 7) and severe (8, 9). COLV 3D reconstruction was performed by confocal microscopy, COL Vα1 and Vα2 gene expression in fibroblasts of skin and lung was performed in PCR–RT and COLV protein expression by immunoblotting. Results. The structure of COL V fibre in 3D reconstruction showed distorted and strongly thickened fibres in skin and lung fibroblasts with irregular bundles of COL V distributed in parallel and perpendicular arrangements resulting in a dense network in SSc patients compared with thin fibres pattern from the healthy controls. Collagen quantification showed increase of COL V fibres expression in SSc cutaneous fibroblast [82.5 (9.5)% vs 47.5 (9.5)%, P = 0.002] and lung fibroblast 38.87 (2.99)% vs 20.33 (7.50)%, P = 0,002) compared with respective controls. The molecular evaluation demonstrated an increased of COL Vα1 and α2 mRNA expression in SSc fibroblast skin when compared with control [1.375 (0.373) au vs 0.0047 (0.0013) au, P = 0.05). Similar results were observed in lung [1.61 (0.654) vs 0.99 (0.51) au; P = 0.05).The proportion COL Vα1/COL Vα2 mRNA in fibroblast lung and skin was higher in SSc than in controls being the chains ratio 1 : 2. COL V chains from skin and lung fibroblasts presented alteration of molecular weight of the quoted chain. Conclusion. The overexpression and the unusual organization of COLV fibres, besides the biochemical changes, suggest an interference with the fibrillogenesis process in skin and pulmonary fibrosis from SSc patients, reinforcing the participation of this collagen in pathogenesis of SSc and open new therapeutic perspectives for these patients.