TY - JOUR
T1 - Abnormal collagen V deposition in dermis correlates with skin thickening and disease activity in systemic sclerosis
AU - Martin, Patricia
AU - Teodoro, Walcy R.
AU - Velosa, Ana Paula P.
AU - de Morais, Jymenez
AU - Carrasco, Solange
AU - Christmann, Romy B.
AU - Goldenstein-Schainberg, Cláudia
AU - Parra, Edwin R.
AU - Katayama, Maria Lúcia
AU - Sotto, Mirian N.
AU - Capelozzi, Vera L.
AU - Yoshinari, Natalino H.
N1 - Funding Information:
Financial supporters: Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP) and Federico Foundation .
PY - 2012/9
Y1 - 2012/9
N2 - Objective: The 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. Methods: Skin 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. Results: Structurally 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. Conclusion: Increased 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.
AB - Objective: The 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. Methods: Skin 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. Results: Structurally 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. Conclusion: Increased 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.
KW - Modified Rodnan Skin Score
KW - Skin
KW - Systemic sclerosis
KW - Type V collagen
KW - Valentini Disease Activity Index
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U2 - 10.1016/j.autrev.2012.02.017
DO - 10.1016/j.autrev.2012.02.017
M3 - Review article
C2 - 22406224
AN - SCOPUS:84865356287
SN - 1568-9972
VL - 11
SP - 827
EP - 835
JO - Autoimmunity Reviews
JF - Autoimmunity Reviews
IS - 11
ER -