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