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 di stribution of collagen synthesis in normal and systemic sclerosis (SSc ) fibroblast populations in order to determine the extent of activatio n in SSc populations, Methods. We used quantitative in situ hybridizat ion to assess the population distribution of type I collagen synthesis , Fibroblast cultures were derived from both clinically involved and u ninvolved 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 a dults were heterogeneous for distribution of alpha 1(I) procollagen mR NA when assessed by in situ hybridization, with a wide range of grains per cell, Ire contrast, clones of neonatal fibroblasts showed a relat ively homogeneous distribution of grain counts. Involved SSc skin fibr oblasts had a larger proportion of cells in the high collagen-producin g mRNA subpopulation (mean +/- SEM 28.4 +/- 6.85%), compared with norm al 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%), wh ile normal fibroblasts had a majority of the cells in this subpopulati on (53.5 +/- 8.68%),Conclusion. These results suggest that only a spec ific subset of fibroblasts are activated in SSc, as evidenced by an in creased proportion of cells,vith high levels of alpha 1(I) procollagen mRNA, Differences between the SSc and normal fibroblast populations a ppeared to be quantitative rather than qualitative. This may be a resu lt of either clonal selection or selective activation in the pathogene sis of SSc.