title: Abnormal collagen V deposition in dermis correlates with skin thickening and disease activity in systemic sclerosis.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Rheumatology, Universidade de São Paulo, São Paulo-SP, Brazil.
authors.forename: Patricia
authors.initials: P
authors.lastname: Martin
authors.forename: Walcy R
authors.initials: WR
authors.lastname: Teodoro
authors.forename: Ana Paula P
authors.initials: AP
authors.lastname: Velosa
authors.forename: Jymenez
authors.initials: J
authors.lastname: de Morais
authors.forename: Solange
authors.initials: S
authors.lastname: Carrasco
authors.forename: Romy B
authors.initials: RB
authors.lastname: Christmann
authors.forename: Cláudia
authors.initials: C
authors.lastname: Goldenstein-Schainberg
authors.forename: Edwin R
authors.initials: ER
authors.lastname: Parra
authors.forename: Maria Lúcia
authors.initials: ML
authors.lastname: Katayama
authors.forename: Mirian N
authors.initials: MN
authors.lastname: Sotto
authors.forename: Vera L
authors.initials: VL
authors.lastname: Capelozzi
authors.forename: Natalino H
authors.initials: NH
authors.lastname: Yoshinari
mesh_terms: D000328:Adult; D001706:Biopsy; D016022:Case-Control Studies; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D024062:Collagen Type V / Q000235:genetics / Q000378:metabolism*; D020405:Dermis / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D012595:Scleroderma, Systemic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D012720:Severity of Illness Index; D012867:Skin / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D024062:Collagen Type V; D003094:Collagen