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Biochem J. Mar 15, 1997; 322(Pt 3): 809–814.
PMCID: PMC1218259

Degradation of decorin by matrix metalloproteinases: identification of the cleavage sites, kinetic analyses and transforming growth factor-beta1 release.

Abstract

Decorin (DCN) is a ubiquitous proteoglycan comprised of a core protein attached to a single dermatan/chondroitin sulphate glycosaminoglycan chain. It may play a role in regulation of collagen fibrillogenesis and function as a reservoir of transforming growth factor beta (TGF-beta) in the extracellular milieu. We have examined the susceptibility of DCN to five different matrix metalloproteinases (MMPs): MMP-1 (tissue collagenase), MMP-2 (gelatinase A), MMP-3 (stromelysin 1), MMP-7 (matrilysin) and MMP-9 (gelatinase B). MMP-2 and MMP-3 digest DCN into seven major fragments in a similar pattern. The N-terminal sequence of the two fragments generated by MMP-2 and MMP-3 is Leu211-Lys-Gly-Leu-Asn, but that of the others is Asp1-Glu-Ala-Ser-Gly. MMP-7 cleaves DCN into three major fragments which have the N-termini Asp1-Glu-Ala-Ser-Gly, Glu2-Ala-Ser-Gly-Ile and Leu244-His-Leu-Asp-Asn. Activities of MMP-1 and MMP-9 against DCN are negligible. The values of Km for the MMPs capable of degrading DCN are very similar (10-12 microM), but the kcat/Km value for MMP-7 (30.5 microM-1.h-1) is 4.5-fold higher than those for MMP-2 and MMP-3. Incubation of a DCN-TGF-beta1 complex with MMP-2, -3 or -7 results in release of TGF-beta1 from the complex. These data indicate proteolytic degradation of DCN by MMP-2, MMP-3 and MMP-7, and suggest the possibility that, under pathophysiological conditions, the digestion by the MMPs may induce tissue reactions mediated by TGF-beta1 released from DCN in the connective tissues.

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Selected References

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  • Kresse H, Hausser H, Schönherr E, Bittner K. Biosynthesis and interactions of small chondroitin/dermatan sulphate proteoglycans. Eur J Clin Chem Clin Biochem. 1994 Apr;32(4):259–264. [PubMed]
  • Yamaguchi Y, Ruoslahti E. Expression of human proteoglycan in Chinese hamster ovary cells inhibits cell proliferation. Nature. 1988 Nov 17;336(6196):244–246. [PubMed]
  • Heinegård D, Paulsson M, Inerot S, Carlström C. A novel low-molecular weight chondroitin sulphate proteoglycan isolated from cartilage. Biochem J. 1981 Aug 1;197(2):355–366. [PMC free article] [PubMed]
  • Krusius T, Ruoslahti E. Primary structure of an extracellular matrix proteoglycan core protein deduced from cloned cDNA. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7683–7687. [PMC free article] [PubMed]
  • Damle SP, Cöster L, Gregory JD. Proteodermatan sulfate isolated from pig skin. J Biol Chem. 1982 May 25;257(10):5523–5527. [PubMed]
  • Rosenberg LC, Choi HU, Tang LH, Johnson TL, Pal S, Webber C, Reiner A, Poole AR. Isolation of dermatan sulfate proteoglycans from mature bovine articular cartilages. J Biol Chem. 1985 May 25;260(10):6304–6313. [PubMed]
  • Yamaguchi Y, Mann DM, Ruoslahti E. Negative regulation of transforming growth factor-beta by the proteoglycan decorin. Nature. 1990 Jul 19;346(6281):281–284. [PubMed]
  • Hildebrand A, Romarís M, Rasmussen LM, Heinegård D, Twardzik DR, Border WA, Ruoslahti E. Interaction of the small interstitial proteoglycans biglycan, decorin and fibromodulin with transforming growth factor beta. Biochem J. 1994 Sep 1;302(Pt 2):527–534. [PMC free article] [PubMed]
  • Will H, Hinzmann B. cDNA sequence and mRNA tissue distribution of a novel human matrix metalloproteinase with a potential transmembrane segment. Eur J Biochem. 1995 Aug 1;231(3):602–608. [PubMed]
  • Takino T, Sato H, Shinagawa A, Seiki M. Identification of the second membrane-type matrix metalloproteinase (MT-MMP-2) gene from a human placenta cDNA library. MT-MMPs form a unique membrane-type subclass in the MMP family. J Biol Chem. 1995 Sep 29;270(39):23013–23020. [PubMed]
  • Zhang J, Fujimoto N, Iwata K, Sakai T, Okada Y, Hayakawa T. A one-step sandwich enzyme immunoassay for human matrix metalloproteinase 1 (interstitial collagenase) using monoclonal antibodies. Clin Chim Acta. 1993 Oct 15;219(1-2):1–14. [PubMed]
  • Okada Y, Morodomi T, Enghild JJ, Suzuki K, Yasui A, Nakanishi I, Salvesen G, Nagase H. Matrix metalloproteinase 2 from human rheumatoid synovial fibroblasts. Purification and activation of the precursor and enzymic properties. Eur J Biochem. 1990 Dec 27;194(3):721–730. [PubMed]
  • Okada Y, Harris ED, Jr, Nagase H. The precursor of a metalloendopeptidase from human rheumatoid synovial fibroblasts. Purification and mechanisms of activation by endopeptidases and 4-aminophenylmercuric acetate. Biochem J. 1988 Sep 15;254(3):731–741. [PMC free article] [PubMed]
  • Imai K, Yokohama Y, Nakanishi I, Ohuchi E, Fujii Y, Nakai N, Okada Y. Matrix metalloproteinase 7 (matrilysin) from human rectal carcinoma cells. Activation of the precursor, interaction with other matrix metalloproteinases and enzymic properties. J Biol Chem. 1995 Mar 24;270(12):6691–6697. [PubMed]
  • Okada Y, Gonoji Y, Naka K, Tomita K, Nakanishi I, Iwata K, Yamashita K, Hayakawa T. Matrix metalloproteinase 9 (92-kDa gelatinase/type IV collagenase) from HT 1080 human fibrosarcoma cells. Purification and activation of the precursor and enzymic properties. J Biol Chem. 1992 Oct 25;267(30):21712–21719. [PubMed]
  • Welgus HG, Jeffrey JJ, Eisen AZ. The collagen substrate specificity of human skin fibroblast collagenase. J Biol Chem. 1981 Sep 25;256(18):9511–9515. [PubMed]
  • Fukushima D, Bützow R, Hildebrand A, Ruoslahti E. Localization of transforming growth factor beta binding site in betaglycan. Comparison with small extracellular matrix proteoglycans. J Biol Chem. 1993 Oct 25;268(30):22710–22715. [PubMed]
  • Sawhney RS, Hering TM, Sandell LJ. Biosynthesis of small proteoglycan II (decorin) by chondrocytes and evidence for a procore protein. J Biol Chem. 1991 May 15;266(14):9231–9240. [PubMed]
  • Schmidt G, Hausser H, Kresse H. Extracellular accumulation of small dermatan sulphate proteoglycan II by interference with the secretion-recapture pathway. Biochem J. 1990 Mar 1;266(2):591–595. [PMC free article] [PubMed]
  • Hausser H, Hoppe W, Rauch U, Kresse H. Endocytosis of a small dermatan sulphate proteoglycan. Identification of binding proteins. Biochem J. 1989 Oct 1;263(1):137–142. [PMC free article] [PubMed]
  • Imai K, Kusakabe M, Sakakura T, Nakanishi I, Okada Y. Susceptibility of tenascin to degradation by matrix metalloproteinases and serine proteinases. FEBS Lett. 1994 Sep 26;352(2):216–218. [PubMed]
  • Imai K, Shikata H, Okada Y. Degradation of vitronectin by matrix metalloproteinases-1, -2, -3, -7 and -9. FEBS Lett. 1995 Aug 7;369(2-3):249–251. [PubMed]
  • Sires UI, Griffin GL, Broekelmann TJ, Mecham RP, Murphy G, Chung AE, Welgus HG, Senior RM. Degradation of entactin by matrix metalloproteinases. Susceptibility to matrilysin and identification of cleavage sites. J Biol Chem. 1993 Jan 25;268(3):2069–2074. [PubMed]
  • Nguyen Q, Murphy G, Hughes CE, Mort JS, Roughley PJ. Matrix metalloproteinases cleave at two distinct sites on human cartilage link protein. Biochem J. 1993 Oct 15;295(Pt 2):595–598. [PMC free article] [PubMed]
  • Murphy G, Cockett MI, Ward RV, Docherty AJ. Matrix metalloproteinase degradation of elastin, type IV collagen and proteoglycan. A quantitative comparison of the activities of 95 kDa and 72 kDa gelatinases, stromelysins-1 and -2 and punctuated metalloproteinase (PUMP). Biochem J. 1991 Jul 1;277(Pt 1):277–279. [PMC free article] [PubMed]
  • Johnstone B, Markopoulos M, Neame P, Caterson B. Identification and characterization of glycanated and non-glycanated forms of biglycan and decorin in the human intervertebral disc. Biochem J. 1993 Jun 15;292(Pt 3):661–666. [PMC free article] [PubMed]
  • Witsch-Prehm P, Miehlke R, Kresse H. Presence of small proteoglycan fragments in normal and arthritic human cartilage. Arthritis Rheum. 1992 Sep;35(9):1042–1052. [PubMed]
  • Scholzen T, Solursh M, Suzuki S, Reiter R, Morgan JL, Buchberg AM, Siracusa LD, Iozzo RV. The murine decorin. Complete cDNA cloning, genomic organization, chromosomal assignment, and expression during organogenesis and tissue differentiation. J Biol Chem. 1994 Nov 11;269(45):28270–28281. [PubMed]
  • Schönherr E, Hausser H, Beavan L, Kresse H. Decorin-type I collagen interaction. Presence of separate core protein-binding domains. J Biol Chem. 1995 Apr 14;270(15):8877–8883. [PubMed]
  • Svensson L, Heinegård D, Oldberg A. Decorin-binding sites for collagen type I are mainly located in leucine-rich repeats 4-5. J Biol Chem. 1995 Sep 1;270(35):20712–20716. [PubMed]
  • Vogel KG, Koob TJ, Fisher LW. Characterization and interactions of a fragment of the core protein of the small proteoglycan (PGII) from bovine tendon. Biochem Biophys Res Commun. 1987 Oct 29;148(2):658–663. [PubMed]
  • Takeuchi Y, Kodama Y, Matsumoto T. Bone matrix decorin binds transforming growth factor-beta and enhances its bioactivity. J Biol Chem. 1994 Dec 23;269(51):32634–32638. [PubMed]
  • Hausser H, Gröning A, Hasilik A, Schönherr E, Kresse H. Selective inactivity of TGF-beta/decorin complexes. FEBS Lett. 1994 Oct 24;353(3):243–245. [PubMed]
  • Rosenberg LC, Choi HU, Poole AR, Lewandowska K, Culp LA. Biological roles of dermatan sulphate proteoglycans. Ciba Found Symp. 1986;124:47–68. [PubMed]
  • Miosge N, Flachsbart K, Goetz W, Schultz W, Kresse H, Herken R. Light and electron microscopical immunohistochemical localization of the small proteoglycan core proteins decorin and biglycan in human knee joint cartilage. Histochem J. 1994 Dec;26(12):939–945. [PubMed]
  • Cs-Szabó G, Roughley PJ, Plaas AH, Glant TT. Large and small proteoglycans of osteoarthritic and rheumatoid articular cartilage. Arthritis Rheum. 1995 May;38(5):660–668. [PubMed]
  • Okuda S, Languino LR, Ruoslahti E, Border WA. Elevated expression of transforming growth factor-beta and proteoglycan production in experimental glomerulonephritis. Possible role in expansion of the mesangial extracellular matrix. J Clin Invest. 1990 Aug;86(2):453–462. [PMC free article] [PubMed]
  • Border WA, Okuda S, Languino LR, Sporn MB, Ruoslahti E. Suppression of experimental glomerulonephritis by antiserum against transforming growth factor beta 1. Nature. 1990 Jul 26;346(6282):371–374. [PubMed]
  • Marti HP, Lee L, Kashgarian M, Lovett DH. Transforming growth factor-beta 1 stimulates glomerular mesangial cell synthesis of the 72-kd type IV collagenase. Am J Pathol. 1994 Jan;144(1):82–94. [PMC free article] [PubMed]
  • Border WA, Noble NA, Yamamoto T, Harper JR, Yamaguchi Y u, Pierschbacher MD, Ruoslahti E. Natural inhibitor of transforming growth factor-beta protects against scarring in experimental kidney disease. Nature. 1992 Nov 26;360(6402):361–364. [PubMed]

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