Fibroblast heterogeneity and prostaglandin regulation of subpopulations.

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.