Heterogeneity of collagen synthesis in normal and systemic sclerosis skin fibroblasts. Increased proportion of high collagen-producing cells in systemic sclerosis fibroblasts.
OBJECTIVE
The goal of this study was to quantitatively analyze the distribution of collagen synthesis in normal and systemic sclerosis (SSc) fibroblast populations in order to determine the extent of activation in SSc populations.


METHODS
We used quantitative in situ hybridization to assess the population distribution of type I collagen synthesis. Fibroblast cultures were derived from both clinically involved and uninvolved skin regions of patients with SSc, and from healthy adults, and assessed for levels of alpha 1(I) procollagen messenger RNA (mRNA).


RESULTS
Dermal fibroblasts from both patients with SSc and normal adults were heterogeneous for distribution of alpha 1(I) procollagen mRNA when assessed by in situ hybridization, with a wide range of grains per cell. In contrast, clones of neonatal fibroblasts showed a relatively homogeneous distribution of grain counts. Involved SSc skin fibroblasts had a larger proportion of cells in the high collagen-producing mRNA subpopulation (mean +/- SEM 28.4 +/- 6.85%), compared with normal fibroblasts (1.75 +/- 1.44%) and uninvolved fibroblasts (9.6 +/- 6.73%). Conversely, within the low collagen-producing mRNA subpopulation, involved fibroblasts had a smaller proportion of cells (mean +/- SEM 14.0 +/- 5.63%) than did uninvolved fibroblasts (37.8 +/- 13.69%), while normal fibroblasts had a majority of the cells in this subpopulation (53.5 +/- 8.68%).


CONCLUSIONS
These results suggest that only a specific subset of fibroblasts are activated in SSc, as evidence by an increased proportion of cells with high levels of alpha 1(I) procollagen mRNA. Differences between the SSc and normal fibroblast populations appeared to be quantitative rather than qualitative. This may be a result of either clonal selection or selective activation in the pathogenesis of SSc.
Jelaska
A
A
Boston University School of Medicine, MA 02118, USA.
Arakawa
M
M
Broketa
G
G
Korn
J H
JH
D000328:Adult; D000368:Aged; D015152:Blotting, Northern; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D005347:Fibroblasts / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology*; D018740:Genetic Heterogeneity; D006801:Humans; D017403:In Situ Hybridization; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D012595:Scleroderma, Systemic / Q000235:genetics*; D012867:Skin / Q000166:cytology
D012333:RNA, Messenger; D003094:Collagen