Abnormal collagen V deposition in dermis correlates with skin thickening and disease activity in systemic sclerosis

ObjectiveThe physiological and mechanical properties of the skin, the primary tissue affected by systemic sclerosis, depend on the assembly of collagen types I, III and V, which form heterotypic fibers. Collagen V (COLV) regulates heterotypic fiber diameter, and the maintenance of its properties is important for maintaining normal tissue architecture and function. Based on a COLV-induced experimental SSc model, in which overexpression of abnormal COLV was a prominent feature, we assumed that this abnormality could be present in SSc patients and could be correlated to disease duration, skin thickening and disease activity.MethodsSkin biopsies from 18 patients (6 early-stage and 12 late-stage) and 10 healthy controls were studied. Skin thickening assessment was performed with the Modified Rodnan Skin Score (MRSS), and activity was calculated using the Valentini Disease Activity Index. Morphology, morphometry of COLV deposition in dermis, as well as, quantitative RT-PCR and 3D-reconstruction of the dermal fibroblast culture were performed.ResultsStructurally abnormal COLV was overexpressed in SSc skin, mainly in the early stages of the disease, when compared to normal controls and late-stage. A positive correlation between COLV expression and MRSS and disease activity was observed. Collagen V alpha-1 and alpha-2 mRNA expression levels were higher in SSc. Tridimensional reconstruction of SSc dermal heterotypic fibers confirmed the presence of atypical COLV.ConclusionIncreased synthesis of abnormal COLV and its correlation with disease stage, activity and MRSS suggest that this collagen can be a possible trigger involved in the pathogenesis of SSc.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► COLV histological profile was evaluated in systemic sclerosis patients and controls. ► COLV quantification was done by histomorphometry and RT-PCR. ► COLV is overexpressed in the dermis of SSc patients, especially in the early-stage. ► A positive correlation between COLV and MRSS and disease activity was observed. ► Dermal fibroblasts culture 3D reconstruction showed a morphologically abnormal COLV.