Fibroblast heterogeneity and prostaglandin regulation of subpopulations

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Abstract
The effects of prostaglandin E(2) (PGE(2)) upon the synthesis of protein and DNA, and membrane transport of proline and thymidine, by human diploid fibroblasts were studied. At a concentration range of 1-10 muM, PGE(2) inhibited protein synthesis and membrane transport by 45-50%. Serum-activated DNA synthesis and thymidine transport were also inhibited by approximately 50% in cells made quiescent and synchronous by serum deprivation. To determine whether prostaglandin inhibits some of the cells completely or all of the cells partially, radioautographic and cell-counting experiments were done. In cultures pulse-labeled with [(3)H]thymidine 12-33 hr after serum activation, prostaglandin exposure reduced the number of labeled nuclei by 42%. Sixty-five hours after serum activation, the total cell numbers present in the PGE(2)-exposed cultures were reduced by 25%. Furthermore, in the fibroblast cultures derived from cells previously maintained in 10 muM PGE(2) for 14 days, PGE(2) had no effect on DNA synthesis, indicating that the PGE(2)-sensitive cells had disappeared from the cultures. Thus, PGE(2) appears to inhibit growth and synthesis of a subpopulation of cells while not affecting the remaining insensitive cells. Prostaglandins may play an important role in connective-tissue differentiation and in some pathologic alterations by regulating fibroblast subpopulations.