Collagen turnover is diminished by different clones of skin fibroblasts from early- but not late-stage systemic sclerosis.
To investigate collagen turnover and proliferation in dermal fibroblasts from patients with systemic sclerosis (SSc) and their relationship with disease duration and cellular subpopulations, SSc patients were grouped by disease duration (less than 2.5 years or more than 7 years). Control and SSc fibroblasts were obtained from skin biopsies. Collagen biosynthesis was determined by [14C]-proline uptake. Type I/III collagens, gelatinolytic activity, and tissue inhibitors of metalloproteinases (TIMP)-1 and -2 were evaluated by electrophoresis, zymography, and enzyme-linked immunosorbent assay, respectively. Total collagen synthesis and the levels of alpha1(I), alpha2(I), and alpha1(III) chains, as well as TIMP-1 and proliferation were increased in fibroblasts only from patients with early-stage SSc. Gelatinolytic activity did not vary among the groups. This metabolic condition favors a higher local fibroblast population and is characterized by a heterogeneous clonal response in which the majority exhibited higher levels of collagen and TIMP-1 synthesis as well as an increase in their proliferation patterns involving hyper-reactive fibroblast subsets.
Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Tlalpan, 14000, Mexico City, Mexico.
Camilo S
CS
Zurita-Salinas
Edgar
E
Krötzsch
Lino
L
Díaz de León
Jorge
J
Alcocer-Varela
D000328:Adult; D017668:Age of Onset; D002250:Carbon Radioisotopes; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D002999:Clone Cells / Q000378:metabolism; D003094:Collagen / Q000378:metabolism*; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D018450:Disease Progression; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D018093:Gelatinases / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D011392:Proline / Q000378:metabolism; D012595:Scleroderma, Systemic / Q000378:metabolism* / Q000503:physiopathology*; D012867:Skin / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism
C439971:COL3A1 protein, human; D002250:Carbon Radioisotopes; D024042:Collagen Type I; D024061:Collagen Type III; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D003094:Collagen; D011392:Proline; D018093:Gelatinases