[1809] Histoarchitecture and Biochemical Profile of Collagen V in Skin and Lung Fibroblasts Culture from Patients with SSc Indicate a Defect in Fibrilogenesis.

Walcy R Teodoro, Ana Paula P Velosa, Romy BC Souza, Solange Carrasco, Jymenez de Morais, Patricia Martin, Edwin R Parra, Natalino H Yoshinari, Vera L Capelozzi. Faculdade de Medicina da Universidade de São Paulo, Brazil

Background: The type V collagen (COLV) mutations is involved in collagen vascular diseases, such as systemic sclerosis (SSc), in which an unusual accumulation of this collagen was demonstrated (Pathol Res Pract 200:681, 2004). In this context, our purpose was to analyze the tridimensional reconstruction (3D) and biochemical profile of COLV alpha-1 and alpha-2 chains in skin and lung fibroblasts culture from patients with SSc.
Design: We analyzed tridimensional reconstruction (3D), biochemical profile and RT-PCR of COLV alpha-1 and alpha-2 chains in skin and lung fibroblast of 5 and 14 patients with SSc without pulmonary hypertension, respectively. Five and 8 healthy control skin and lung fibroblasts were obtained from thorax region during mamoplasty and during lung. COLV 3D reconstruction was performed by confocal microscopy and COL V chain expression was analyzed by immunobloting and Real Time RT-PCR.
Results: The structure of COL V fiber in 3D reconstruction showed distorted and strongly thickened fibers in skin and lung fibroblasts from SSc patients compared with thin fibers pattern from the healthy controls. In skin fibroblasts was observed the biochemical profile of the COLV with the increase expression of the alpha-1 and alpha-2 chains related with controls (p=0.02, p=0.01, respectively). In SSc lungs fibroblasts we found increase in both, alpha 1 (1.32±0.34) and 2 (0.86±0.19) chains mRNA expression when compared with alpha 1 (0.50±0.10) and 2 (0.11±0.05) chains of control group. COL V chains from skin and lung fibroblasts presented alteration of molecular weight of the quoted chain.
Conclusions: The overexpression and the unusual organization of COLV fibers, 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.
Financial support: FAPESP, CNPq.
Category: Pulmonary

Wednesday, March 2, 2011 9:30 AM

Poster Session V # 260, Wednesday Morning

 

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