Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1987 Nov;80(5):1280–1288. doi: 10.1172/JCI113203

Regulation of the expression of tissue inhibitor of metalloproteinases and collagenase by retinoids and glucocorticoids in human fibroblasts.

S D Clark 1, D K Kobayashi 1, H G Welgus 1
PMCID: PMC442381  PMID: 2824558

Abstract

The regulation of the expression of interstitial collagenase and tissue inhibitor of metalloproteinases (TIMP) was examined in response to both retinoid compounds and glucocorticoids. Effective retinoids induced a dose-dependent, specific increase in the production of TIMP of approximately two- to threefold by monolayer cultures of human fibroblasts derived from various tissues, while simultaneously causing a decrease in collagenase secretion of similar magnitude. These effects were apparent by 8-12 h in culture and disappeared within 24 h after the withdrawal of retinoid compounds. The retinoid effect on TIMP production was mediated via an increased biosynthesis of new inhibitor protein. Similarly, increased steady state levels of TIMP messenger RNA (mRNA) accompanied by decreased quantities of collagenase mRNA were demonstrated, suggesting transcriptional control of the retinoid action. The data suggest that retinoids co-regulate the expression of collagenase and TIMP, and do so in an inverse manner. Dexamethasone caused a dose-dependent, specific decrease in collagenase production without altering the biosynthesis of TIMP. These findings were paralleled by a marked reduction in collagenase mRNA, without any accompanying change in TIMP mRNA. Therefore, TIMP and collagenase expression appear to be independently modulated by glucocorticoids.

Full text

PDF
1280

Images in this article

1284Image
on p.1284
1285Image
on p.1285
1285Image
on p.1285
1286Image
on p.1286
1286Image
on p.1286

Selected References

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

  1. Bauer E. A., Cooper T. W., Huang J. S., Altman J., Deuel T. F. Stimulation of in vitro human skin collagenase expression by platelet-derived growth factor. Proc Natl Acad Sci U S A. 1985 Jun;82(12):4132–4136. doi: 10.1073/pnas.82.12.4132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bauer E. A., Cooper T. W., Tucker D. R., Esterly N. B. Phenytoin therapy of recessive dystrophic epidermolysis bullosa. Clinical trial and proposed mechanism of action on collagenase. N Engl J Med. 1980 Oct 2;303(14):776–781. doi: 10.1056/NEJM198010023031402. [DOI] [PubMed] [Google Scholar]
  3. Bauer E. A., Kronberger A., Valle K. J., Jeffrey J. J., Eisen A. Z. Glucocorticoid modulation of collagenase expression in human skin fibroblast cultures. Evidence for pre-translational inhibition. Biochim Biophys Acta. 1985 Jun 24;825(2):227–235. doi: 10.1016/0167-4781(85)90107-1. [DOI] [PubMed] [Google Scholar]
  4. Bauer E. A., Seltzer J. L., Eisen A. Z. Inhibition of collagen degradative enzymes by retinoic acid in vitro. J Am Acad Dermatol. 1982 Apr;6(4 Pt 2 Suppl):603–607. doi: 10.1016/s0190-9622(82)70049-0. [DOI] [PubMed] [Google Scholar]
  5. Bauer E. A., Seltzer J. L., Eisen A. Z. Retinoic acid inhibition of collagenase and gelatinase expression in human skin fibroblast cultures. Evidence for a dual mechanism. J Invest Dermatol. 1983 Aug;81(2):162–169. doi: 10.1111/1523-1747.ep12543590. [DOI] [PubMed] [Google Scholar]
  6. Baxter J. D., Funder J. W. Hormone receptors. N Engl J Med. 1979 Nov 22;301(21):1149–1161. doi: 10.1056/NEJM197911223012104. [DOI] [PubMed] [Google Scholar]
  7. Brinckerhoff C. E., Gross R. H., Nagase H., Sheldon L., Jackson R. C., Harris E. D., Jr Increased level of translatable collagenase messenger ribonucleic acid in rabbit synovial fibroblasts treated with phorbol myristate acetate or crystals of monosodium urate monohydrate. Biochemistry. 1982 May 25;21(11):2674–2679. doi: 10.1021/bi00540a015. [DOI] [PubMed] [Google Scholar]
  8. Brinckerhoff C. E., McMillan R. M., Dayer J. M., Harris E. D., Jr Inhibition by retinoic acid of collagenase production in rheumatoid synovial cells. N Engl J Med. 1980 Aug 21;303(8):432–436. doi: 10.1056/NEJM198008213030805. [DOI] [PubMed] [Google Scholar]
  9. Brinckerhoff C. E., Plucinska I. M., Sheldon L. A., O'Connor G. T. Half-life of synovial cell collagenase mRNA is modulated by phorbol myristate acetate but not by all-trans-retinoic acid or dexamethasone. Biochemistry. 1986 Oct 21;25(21):6378–6384. doi: 10.1021/bi00369a006. [DOI] [PubMed] [Google Scholar]
  10. Carmichael D. F., Sommer A., Thompson R. C., Anderson D. C., Smith C. G., Welgus H. G., Stricklin G. P. Primary structure and cDNA cloning of human fibroblast collagenase inhibitor. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2407–2411. doi: 10.1073/pnas.83.8.2407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cawston T. E., Murphy G., Mercer E., Galloway W. A., Hazleman B. L., Reynolds J. J. The interaction of purified rabbit bone collagenase with purified rabbit bone metalloproteinase inhibitor. Biochem J. 1983 May 1;211(2):313–318. doi: 10.1042/bj2110313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  13. Clark S. D., Wilhelm S. M., Stricklin G. P., Welgus H. G. Coregulation of collagenase and collagenase inhibitor production by phorbol myristate acetate in human skin fibroblasts. Arch Biochem Biophys. 1985 Aug 15;241(1):36–44. doi: 10.1016/0003-9861(85)90358-3. [DOI] [PubMed] [Google Scholar]
  14. Cooper T. W., Bauer E. A., Eisen A. Z. Enzyme-linked immunosorbent assay for human skin collagenase. Coll Relat Res. 1983 May;3(3):205–215. doi: 10.1016/s0174-173x(83)80004-1. [DOI] [PubMed] [Google Scholar]
  15. Cooper T. W., Eisen A. Z., Stricklin G. P., Welgus H. G. Platelet-derived collagenase inhibitor: characterization and subcellular localization. Proc Natl Acad Sci U S A. 1985 May;82(9):2779–2783. doi: 10.1073/pnas.82.9.2779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Dayer J. M., Bréard J., Chess L., Krane S. M. Participation of monocyte-macrophages and lymphocytes in the production of a factor that stimulates collagenase and prostaglandin release by rheumatoid synovial cells. J Clin Invest. 1979 Nov;64(5):1386–1392. doi: 10.1172/JCI109596. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Docherty A. J., Lyons A., Smith B. J., Wright E. M., Stephens P. E., Harris T. J., Murphy G., Reynolds J. J. Sequence of human tissue inhibitor of metalloproteinases and its identity to erythroid-potentiating activity. Nature. 1985 Nov 7;318(6041):66–69. doi: 10.1038/318066a0. [DOI] [PubMed] [Google Scholar]
  18. Eisen A. Z., Jeffrey J. J., Gross J. Human skin collagenase. Isolation and mechanism of attack on the collagen molecule. Biochim Biophys Acta. 1968 Mar 25;151(3):637–645. doi: 10.1016/0005-2744(68)90010-7. [DOI] [PubMed] [Google Scholar]
  19. Goldberg G. I., Wilhelm S. M., Kronberger A., Bauer E. A., Grant G. A., Eisen A. Z. Human fibroblast collagenase. Complete primary structure and homology to an oncogene transformation-induced rat protein. J Biol Chem. 1986 May 15;261(14):6600–6605. [PubMed] [Google Scholar]
  20. Gross J., Nagai Y. Specific degradation of the collagen molecule by tadpole collagenolytic enzyme. Proc Natl Acad Sci U S A. 1965 Oct;54(4):1197–1204. doi: 10.1073/pnas.54.4.1197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. King J., Laemmli U. K. Polypeptides of the tail fibres of bacteriophage T4. J Mol Biol. 1971 Dec 28;62(3):465–477. doi: 10.1016/0022-2836(71)90148-3. [DOI] [PubMed] [Google Scholar]
  22. Koob T. J., Jeffrey J. J., Eisen A. Z., Bauer E. A. Hormonal interactions in mammalian collagenase regulation. Comparative studies in human skin and rat uterus. Biochim Biophys Acta. 1980 Apr 17;629(1):13–23. doi: 10.1016/0304-4165(80)90260-3. [DOI] [PubMed] [Google Scholar]
  23. Koob T. J., Jeffrey J. J., Eisen A. Z. Regulation of human skin collagenase activity by hydrocortisone and dexamethasone in organ culture. Biochem Biophys Res Commun. 1974 Dec 11;61(3):1083–1088. doi: 10.1016/0006-291x(74)90266-6. [DOI] [PubMed] [Google Scholar]
  24. Laskey R. A., Mills A. D. Quantitative film detection of 3H and 14C in polyacrylamide gels by fluorography. Eur J Biochem. 1975 Aug 15;56(2):335–341. doi: 10.1111/j.1432-1033.1975.tb02238.x. [DOI] [PubMed] [Google Scholar]
  25. McGuire M. B., Murphy G., Reynolds J. J., Russell R. G. Production of collagenase and inhibitor (TIMP) by normal, rheumatoid and osteoarthritic synovium in vitro: effects of hydrocortisone and indomethacin. Clin Sci (Lond) 1981 Dec;61(6):703–710. doi: 10.1042/cs0610703. [DOI] [PubMed] [Google Scholar]
  26. Mizel S. B., Dayer J. M., Krane S. M., Mergenhagen S. E. Stimulation of rheumatoid synovial cell collagenase and prostaglandin production by partially purified lymphocyte-activating factor (interleukin 1). Proc Natl Acad Sci U S A. 1981 Apr;78(4):2474–2477. doi: 10.1073/pnas.78.4.2474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Murphy G., Reynolds J. J., Werb Z. Biosynthesis of tissue inhibitor of metalloproteinases by human fibroblasts in culture. Stimulation by 12-O-tetradecanoylphorbol 13-acetate and interleukin 1 in parallel with collagenase. J Biol Chem. 1985 Mar 10;260(5):3079–3083. [PubMed] [Google Scholar]
  28. Oikarinen H., Oikarinen A. I., Tan E. M., Abergel R. P., Meeker C. A., Chu M. L., Prockop D. J., Uitto J. Modulation of procollagen gene expression by retinoids. Inhibition of collagen production by retinoic acid accompanied by reduced type I procollagen messenger ribonucleic acid levels in human skin fibroblast cultures. J Clin Invest. 1985 May;75(5):1545–1553. doi: 10.1172/JCI111859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Postlethwaite A. E., Lachman L. B., Mainardi C. L., Kang A. H. Interleukin 1 stimulation of collagenase production by cultured fibroblasts. J Exp Med. 1983 Feb 1;157(2):801–806. doi: 10.1084/jem.157.2.801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sellers A., Murphy G., Meikle M. C., Reynolds J. J. Rabbit bone collagenase inhibitor blocks the activity of other neutral metalloproteinases. Biochem Biophys Res Commun. 1979 Mar 30;87(2):581–587. doi: 10.1016/0006-291x(79)91834-5. [DOI] [PubMed] [Google Scholar]
  31. Stricklin G. P., Welgus H. G. Human skin fibroblast collagenase inhibitor. Purification and biochemical characterization. J Biol Chem. 1983 Oct 25;258(20):12252–12258. [PubMed] [Google Scholar]
  32. Welgus H. G., Campbell E. J., Bar-Shavit Z., Senior R. M., Teitelbaum S. L. Human alveolar macrophages produce a fibroblast-like collagenase and collagenase inhibitor. J Clin Invest. 1985 Jul;76(1):219–224. doi: 10.1172/JCI111949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Welgus H. G., Jeffrey J. J., Eisen A. Z., Roswit W. T., Stricklin G. P. Human skin fibroblast collagenase: interaction with substrate and inhibitor. Coll Relat Res. 1985 Mar;5(2):167–179. doi: 10.1016/s0174-173x(85)80038-8. [DOI] [PubMed] [Google Scholar]
  34. Welgus H. G., Stricklin G. P., Eisen A. Z., Bauer E. A., Cooney R. V., Jeffrey J. J. A specific inhibitor of vertebrate collagenase produced by human skin fibroblasts. J Biol Chem. 1979 Mar 25;254(6):1938–1943. [PubMed] [Google Scholar]
  35. Welgus H. G., Stricklin G. P. Human skin fibroblast collagenase inhibitor. Comparative studies in human connective tissues, serum, and amniotic fluid. J Biol Chem. 1983 Oct 25;258(20):12259–12264. [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES