title: Fibroblast heterogeneity and prostaglandin regulation of subpopulations.
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.
mesh_terms: D001693:Biological Transport, Active; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003470:Culture Media; D004247:DNA / Q000096:biosynthesis*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005881:Gingiva; D006801:Humans; D007700:Kinetics; D011392:Proline / Q000378:metabolism*; D011458:Prostaglandins E / Q000494:pharmacology*; D014176:Protein Biosynthesis; D013936:Thymidine / Q000378:metabolism*
chemical_list: D003470:Culture Media; D011458:Prostaglandins E; D004247:DNA; D011392:Proline; D013936:Thymidine
references.citation: J Biol Chem. 1958 Jul;233(1):184-8
references.pmid: 13563465
references.citation: J Biol Chem. 1976 Sep 25;251(18):5464-71
references.pmid: 965371
references.citation: Arch Intern Med. 1974 Jan;133(1):101-10
references.pmid: 4128189
references.citation: Annu Rev Biochem. 1975;44:669-95
references.pmid: 806254
references.citation: Nat New Biol. 1972 Oct 25;239(95):246
references.pmid: 4507807
references.citation: Science. 1974 Apr 5;184(4132):19-28
references.pmid: 4131281
references.citation: J Clin Invest. 1974 Aug;54(2):378-86
references.pmid: 4367890
references.citation: Prostaglandins. 1974 Dec 10;8(5):377-85
references.pmid: 4375827
references.citation: Connect Tissue Res. 1974;2(3):167-75
references.pmid: 4373210
references.citation: Cell. 1974 Nov;3(3):291-9
references.pmid: 4373172
references.citation: J Pharmacol Exp Ther. 1974 Apr;189(1):213-20
references.pmid: 4362848
references.citation: J Biol Chem. 1972 Sep 25;247(18):5759-64
references.pmid: 4341489
references.citation: Proc Natl Acad Sci U S A. 1971 Jul;68(7):1648-52
references.pmid: 4327009
references.citation: J Exp Med. 1973 Aug 1;138(2):381-93
references.pmid: 4352584
references.citation: Proc Natl Acad Sci U S A. 1973 Dec;70(12):3609-12
references.pmid: 4357882
references.citation: J Clin Invest. 1974 Jan;53(1):297-309
references.pmid: 4357615
references.citation: Endocrinology. 1970 Jun;86(6):1436-40
references.pmid: 4315103
references.citation: Prostaglandins. 1974 Apr 10;6(1):81-5
references.pmid: 4595580
references.citation: J Immunol. 1975 Apr;114(4):1389-93
references.pmid: 46901
references.citation: J Cell Biol. 1974 Jul;62(1):48-53
references.pmid: 4407044
references.citation: Am J Pathol. 1974 Jan;74(1):137-54
references.pmid: 4809311
references.citation: J Pathol. 1973 Nov;111(3):149-58
references.pmid: 4760142
references.citation: J Clin Invest. 1973 Sep;52(9):2259-63
references.pmid: 4727457
references.citation: Life Sci II. 1972 Nov 22;11(22):1101-7
references.pmid: 4663811
references.citation: Biochem Biophys Res Commun. 1972 Jan 31;46(2):364-9
references.pmid: 5057880
references.citation: Proc Natl Acad Sci U S A. 1976 Aug;73(8):2909-12
references.pmid: 1066702
references.citation: Exp Cell Res. 1975 Nov;96(1):31-6
references.pmid: 1193171
references.citation: Prostaglandins. 1975 Oct;10(4):573-9
references.pmid: 1197789
references.citation: J Clin Invest. 1975 Nov;56(5):1181-8
references.pmid: 1184744
references.citation: Nature. 1975 Sep 18;257(5523):227-8
references.pmid: 1161024
references.citation: Proc Soc Exp Biol Med. 1971 May;137(1):331-3
references.pmid: 5581670
references.citation: Dev Biol. 1967 Sep;16(3):203-15
references.pmid: 6056991