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. 1989 Nov;1(1):87–97. doi: 10.1091/mbc.1.1.87

Retinoic acid induces transforming growth factor-beta 2 in cultured keratinocytes and mouse epidermis.

A B Glick 1, K C Flanders 1, D Danielpour 1, S H Yuspa 1, M B Sporn 1
PMCID: PMC361428  PMID: 2519621

Abstract

We have studied the functional interaction between retinoic acid and transforming growth factor-beta (TGF-beta), using the mouse epidermis as a model system. Treatment with retinoic acid increases expression of TGF-beta 2 in cultured keratinocytes in vitro, as well as in the epidermis in vivo. This TGF-beta 2 is secreted in a biologically active form that can bind to surface receptors, in contrast to most other conditions in which TGF-beta is secreted in a latent form. Specific antibodies to TGF-beta 2 partially reverse the ability of retinoic acid to inhibit DNA synthesis in cultured keratinocytes. The regulation of TGF-beta 2 expression by retinoic acid may have important physiological and pharmacological roles in the maintenance of epidermal homeostasis.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akhurst R. J., Fee F., Balmain A. Localized production of TGF-beta mRNA in tumour promoter-stimulated mouse epidermis. Nature. 1988 Jan 28;331(6154):363–365. doi: 10.1038/331363a0. [DOI] [PubMed] [Google Scholar]
  2. Barnard J. A., Beauchamp R. D., Coffey R. J., Moses H. L. Regulation of intestinal epithelial cell growth by transforming growth factor type beta. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1578–1582. doi: 10.1073/pnas.86.5.1578. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brand N., Petkovich M., Krust A., Chambon P., de Thé H., Marchio A., Tiollais P., Dejean A. Identification of a second human retinoic acid receptor. Nature. 1988 Apr 28;332(6167):850–853. doi: 10.1038/332850a0. [DOI] [PubMed] [Google Scholar]
  4. Church G. M., Gilbert W. Genomic sequencing. Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991–1995. doi: 10.1073/pnas.81.7.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Coffey R. J., Jr, Sipes N. J., Bascom C. C., Graves-Deal R., Pennington C. Y., Weissman B. E., Moses H. L. Growth modulation of mouse keratinocytes by transforming growth factors. Cancer Res. 1988 Mar 15;48(6):1596–1602. [PubMed] [Google Scholar]
  6. Danielpour D., Dart L. L., Flanders K. C., Roberts A. B., Sporn M. B. Immunodetection and quantitation of the two forms of transforming growth factor-beta (TGF-beta 1 and TGF-beta 2) secreted by cells in culture. J Cell Physiol. 1989 Jan;138(1):79–86. doi: 10.1002/jcp.1041380112. [DOI] [PubMed] [Google Scholar]
  7. Derynck R., Jarrett J. A., Chen E. Y., Eaton D. H., Bell J. R., Assoian R. K., Roberts A. B., Sporn M. B., Goeddel D. V. Human transforming growth factor-beta complementary DNA sequence and expression in normal and transformed cells. Nature. 1985 Aug 22;316(6030):701–705. doi: 10.1038/316701a0. [DOI] [PubMed] [Google Scholar]
  8. FELL H. B., MELLANBY E. Metaplasia produced in cultures of chick ectoderm by high vitamin A. J Physiol. 1953 Mar;119(4):470–488. doi: 10.1113/jphysiol.1953.sp004860. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Flanders K. C., Roberts A. B., Ling N., Fleurdelys B. E., Sporn M. B. Antibodies to peptide determinants in transforming growth factor beta and their applications. Biochemistry. 1988 Jan 26;27(2):739–746. doi: 10.1021/bi00402a037. [DOI] [PubMed] [Google Scholar]
  10. Flanders K. C., Thompson N. L., Cissel D. S., Van Obberghen-Schilling E., Baker C. C., Kass M. E., Ellingsworth L. R., Roberts A. B., Sporn M. B. Transforming growth factor-beta 1: histochemical localization with antibodies to different epitopes. J Cell Biol. 1989 Feb;108(2):653–660. doi: 10.1083/jcb.108.2.653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fritsch P. O., Pohlin G., Längle U., Elias P. M. Response of epidermal cell proliferation to orally administered aromatic retinoid. J Invest Dermatol. 1981 Sep;77(3):287–291. doi: 10.1111/1523-1747.ep12482459. [DOI] [PubMed] [Google Scholar]
  12. Fuchs E., Green H. Regulation of terminal differentiation of cultured human keratinocytes by vitamin A. Cell. 1981 Sep;25(3):617–625. doi: 10.1016/0092-8674(81)90169-0. [DOI] [PubMed] [Google Scholar]
  13. Giguere V., Ong E. S., Segui P., Evans R. M. Identification of a receptor for the morphogen retinoic acid. Nature. 1987 Dec 17;330(6149):624–629. doi: 10.1038/330624a0. [DOI] [PubMed] [Google Scholar]
  14. Groudine M., Peretz M., Weintraub H. Transcriptional regulation of hemoglobin switching in chicken embryos. Mol Cell Biol. 1981 Mar;1(3):281–288. doi: 10.1128/mcb.1.3.281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Guillemin R., Ling N., Vargo T. Radioimmunoassays for alpha-endorphin and beta-endorphin. Biochem Biophys Res Commun. 1977 Jul 11;77(1):361–366. doi: 10.1016/s0006-291x(77)80205-2. [DOI] [PubMed] [Google Scholar]
  16. Hanks S. K., Armour R., Baldwin J. H., Maldonado F., Spiess J., Holley R. W. Amino acid sequence of the BSC-1 cell growth inhibitor (polyergin) deduced from the nucleotide sequence of the cDNA. Proc Natl Acad Sci U S A. 1988 Jan;85(1):79–82. doi: 10.1073/pnas.85.1.79. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Heine U., Munoz E. F., Flanders K. C., Ellingsworth L. R., Lam H. Y., Thompson N. L., Roberts A. B., Sporn M. B. Role of transforming growth factor-beta in the development of the mouse embryo. J Cell Biol. 1987 Dec;105(6 Pt 2):2861–2876. doi: 10.1083/jcb.105.6.2861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hennings H., Michael D., Cheng C., Steinert P., Holbrook K., Yuspa S. H. Calcium regulation of growth and differentiation of mouse epidermal cells in culture. Cell. 1980 Jan;19(1):245–254. doi: 10.1016/0092-8674(80)90406-7. [DOI] [PubMed] [Google Scholar]
  19. Knabbe C., Lippman M. E., Wakefield L. M., Flanders K. C., Kasid A., Derynck R., Dickson R. B. Evidence that transforming growth factor-beta is a hormonally regulated negative growth factor in human breast cancer cells. Cell. 1987 Feb 13;48(3):417–428. doi: 10.1016/0092-8674(87)90193-0. [DOI] [PubMed] [Google Scholar]
  20. Komm B. S., Terpening C. M., Benz D. J., Graeme K. A., Gallegos A., Korc M., Greene G. L., O'Malley B. W., Haussler M. R. Estrogen binding, receptor mRNA, and biologic response in osteoblast-like osteosarcoma cells. Science. 1988 Jul 1;241(4861):81–84. doi: 10.1126/science.3164526. [DOI] [PubMed] [Google Scholar]
  21. Kopan R., Traska G., Fuchs E. Retinoids as important regulators of terminal differentiation: examining keratin expression in individual epidermal cells at various stages of keratinization. J Cell Biol. 1987 Jul;105(1):427–440. doi: 10.1083/jcb.105.1.427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lawrence D. A., Pircher R., Jullien P. Conversion of a high molecular weight latent beta-TGF from chicken embryo fibroblasts into a low molecular weight active beta-TGF under acidic conditions. Biochem Biophys Res Commun. 1985 Dec 31;133(3):1026–1034. doi: 10.1016/0006-291x(85)91239-2. [DOI] [PubMed] [Google Scholar]
  23. Lawrence D. A., Pircher R., Krycève-Martinerie C., Jullien P. Normal embryo fibroblasts release transforming growth factors in a latent form. J Cell Physiol. 1984 Oct;121(1):184–188. doi: 10.1002/jcp.1041210123. [DOI] [PubMed] [Google Scholar]
  24. Lehnert S. A., Akhurst R. J. Embryonic expression pattern of TGF beta type-1 RNA suggests both paracrine and autocrine mechanisms of action. Development. 1988 Oct;104(2):263–273. doi: 10.1242/dev.104.2.263. [DOI] [PubMed] [Google Scholar]
  25. Madisen L., Webb N. R., Rose T. M., Marquardt H., Ikeda T., Twardzik D., Seyedin S., Purchio A. F. Transforming growth factor-beta 2: cDNA cloning and sequence analysis. DNA. 1988 Jan-Feb;7(1):1–8. doi: 10.1089/dna.1988.7.1. [DOI] [PubMed] [Google Scholar]
  26. Mansbridge J. N., Hanawalt P. C. Role of transforming growth factor beta in the maturation of human epidermal keratinocytes. J Invest Dermatol. 1988 Mar;90(3):336–341. doi: 10.1111/1523-1747.ep12456286. [DOI] [PubMed] [Google Scholar]
  27. Petkovich M., Brand N. J., Krust A., Chambon P. A human retinoic acid receptor which belongs to the family of nuclear receptors. Nature. 1987 Dec 3;330(6147):444–450. doi: 10.1038/330444a0. [DOI] [PubMed] [Google Scholar]
  28. Pfeilschifter J., Mundy G. R. Modulation of type beta transforming growth factor activity in bone cultures by osteotropic hormones. Proc Natl Acad Sci U S A. 1987 Apr;84(7):2024–2028. doi: 10.1073/pnas.84.7.2024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Pircher R., Lawrence D. A., Jullien P. Latent beta-transforming growth factor in nontransformed and Kirsten sarcoma virus-transformed normal rat kidney cells, clone 49F. Cancer Res. 1984 Dec;44(12 Pt 1):5538–5543. [PubMed] [Google Scholar]
  30. Roberts A. B., Anzano M. A., Lamb L. C., Smith J. M., Sporn M. B. New class of transforming growth factors potentiated by epidermal growth factor: isolation from non-neoplastic tissues. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5339–5343. doi: 10.1073/pnas.78.9.5339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Roop D. R., Mehrel T., Krieg T. M., Nakazawa H., Cheng C. K., Yuspa S. H. Keratin expression in mouse epidermal tumors. Carcinog Compr Surv. 1989;11:257–271. [PubMed] [Google Scholar]
  32. Shipley G. D., Pittelkow M. R., Wille J. J., Jr, Scott R. E., Moses H. L. Reversible inhibition of normal human prokeratinocyte proliferation by type beta transforming growth factor-growth inhibitor in serum-free medium. Cancer Res. 1986 Apr;46(4 Pt 2):2068–2071. [PubMed] [Google Scholar]
  33. Smits H. L., Floyd E. E., Jetten A. M. Molecular cloning of gene sequences regulated during squamous differentiation of tracheal epithelial cells and controlled by retinoic acid. Mol Cell Biol. 1987 Nov;7(11):4017–4023. doi: 10.1128/mcb.7.11.4017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Thompson N. L., Flanders K. C., Smith J. M., Ellingsworth L. R., Roberts A. B., Sporn M. B. Expression of transforming growth factor-beta 1 in specific cells and tissues of adult and neonatal mice. J Cell Biol. 1989 Feb;108(2):661–669. doi: 10.1083/jcb.108.2.661. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Tong P. S., Mayes D. M., Wheeler L. A. Differential effects of retinoids on DNA synthesis in calcium-regulated murine epidermal keratinocyte cultures. J Invest Dermatol. 1988 Jun;90(6):861–868. doi: 10.1111/1523-1747.ep12462107. [DOI] [PubMed] [Google Scholar]
  36. Van Obberghen-Schilling E., Kondaiah P., Ludwig R. L., Sporn M. B., Baker C. C. Complementary deoxyribonucleic acid cloning of bovine transforming growth factor-beta 1. Mol Endocrinol. 1987 Oct;1(10):693–698. doi: 10.1210/mend-1-10-693. [DOI] [PubMed] [Google Scholar]
  37. Wakefield L. M., Smith D. M., Flanders K. C., Sporn M. B. Latent transforming growth factor-beta from human platelets. A high molecular weight complex containing precursor sequences. J Biol Chem. 1988 Jun 5;263(16):7646–7654. [PubMed] [Google Scholar]
  38. Wakefield L. M., Smith D. M., Masui T., Harris C. C., Sporn M. B. Distribution and modulation of the cellular receptor for transforming growth factor-beta. J Cell Biol. 1987 Aug;105(2):965–975. doi: 10.1083/jcb.105.2.965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Wang S. Y., LaRosa G. J., Gudas L. J. Molecular cloning of gene sequences transcriptionally regulated by retinoic acid and dibutyryl cyclic AMP in cultured mouse teratocarcinoma cells. Dev Biol. 1985 Jan;107(1):75–86. doi: 10.1016/0012-1606(85)90377-x. [DOI] [PubMed] [Google Scholar]
  40. Yuspa S. H., Elgjo K., Morse M. A., Wiebel F. J. Retinyl acetate modulation of cell growth kinetics and carcinogen--cellular interaction in mouse epidermal cell cultures. Chem Biol Interact. 1977 Mar;16(3):251–264. doi: 10.1016/0009-2797(77)90105-3. [DOI] [PubMed] [Google Scholar]
  41. Yuspa S. H., Harris C. C. Altered differentiation of mouse epidermal cells treated with retinyl acetate in vitro. Exp Cell Res. 1974 May;86(1):95–105. doi: 10.1016/0014-4827(74)90653-3. [DOI] [PubMed] [Google Scholar]
  42. Zelent A., Krust A., Petkovich M., Kastner P., Chambon P. Cloning of murine alpha and beta retinoic acid receptors and a novel receptor gamma predominantly expressed in skin. Nature. 1989 Jun 29;339(6227):714–717. doi: 10.1038/339714a0. [DOI] [PubMed] [Google Scholar]
  43. de Martin R., Haendler B., Hofer-Warbinek R., Gaugitsch H., Wrann M., Schlüsener H., Seifert J. M., Bodmer S., Fontana A., Hofer E. Complementary DNA for human glioblastoma-derived T cell suppressor factor, a novel member of the transforming growth factor-beta gene family. EMBO J. 1987 Dec 1;6(12):3673–3677. doi: 10.1002/j.1460-2075.1987.tb02700.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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