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Article

Targeting the T‑cell membrane type-1 matrix metalloproteinase‑CD44 axis in a transferred type 1 diabetes model in NOD mice

  • Authors:
    • Alexei Y. Savinov
    • Alex Y. Strongin
  • View Affiliations / Copyright

    Affiliations: Sanford Research, University of South Dakota, Sioux Falls, SD 57105, USA, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA
  • Pages: 438-442
    |
    Published online on: November 20, 2012
       https://doi.org/10.3892/etm.2012.821
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Abstract

This study tested the hypothesis that membrane‑tethered type‑1 matrix metalloproteinase (MT1-MMP)-induced proteolysis of T cell CD44 is important for defining the migration and function of autoreactive T cells, including diabetogenic, insulin-specific and Kd-restricted IS-CD8+ cells. To confirm the importance of MT1-MMP proteolysis of CD44 in type 1 diabetes (T1D), the anti-diabetic effects of three MMP inhibitors (3(S)-2,2-dimethyl-4[4-pyridin-4-yloxy-benzenesulfonyl]-thiomorpholine-3-carboxylic acid hydroxamate [AG3340], 2-(4-phenoxyphenylsulfonylmethyl)thiirane [SB-3CT] and epigallocatechin-3-gallate [EGCG]) were compared using an adoptive diabetes transfer model in non-obese diabetic (NOD) mice. Only AG3340 was capable of inhibiting both the activity of MT1-MMP and the shedding of CD44 in T cells; and the transendothelial migration and homing of IS-CD8+ T cells into the pancreatic islets. SB-3CT and EGCG were incapable of inhibiting T cell MT1-MMP efficiently. As a result, AG3340 alone, but not SB-3CT or EGCG, delayed the onset of transferred diabetes in NOD mice. In summary, the results of the present study emphasize that the MT1-MMP-CD44 axis has a unique involvement in T1D development. Accordingly, we suggest that a potent small‑molecule MT1-MMP antagonist is required for the design of novel therapies for T1D.
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1. 

Mathis D, Vence L and Benoist C: beta-Cell death during progression to diabetes. Nature. 414:792–798. 2001. View Article : Google Scholar : PubMed/NCBI

2. 

Butcher EC and Picker LJ: Lymphocyte homing and homeostasis. Science. 272:60–66. 1996. View Article : Google Scholar : PubMed/NCBI

3. 

Nandi A, Estess P and Siegelman M: Bimolecular complex between rolling and firm adhesion receptors required for cell arrest; CD44 association with VLA-4 in T cell extravasation. Immunity. 20:455–465. 2004. View Article : Google Scholar

4. 

Weber C: Novel mechanistic concepts for the control of leukocyte transmigration: specialization of integrins, chemokines, and junctional molecules. J Mol Med (Berl). 81:4–19. 2003.

5. 

Seiki M: Membrane-type 1 matrix metalloproteinase: a key enzyme for tumor invasion. Cancer Lett. 194:1–11. 2003. View Article : Google Scholar : PubMed/NCBI

6. 

Savinov AY, Rozanov DV, Golubkov VS, Wong FS and Strongin AY: Inhibition of membrane type-1 matrix metalloproteinase by cancer drugs interferes with the homing of diabetogenic T cells into the pancreas. J Biol Chem. 280:27755–27758. 2005. View Article : Google Scholar : PubMed/NCBI

7. 

Suenaga N, Mori H, Itoh Y and Seiki M: CD44 binding through the hemopexin-like domain is critical for its shedding by membrane-type 1 matrix metalloproteinase. Oncogene. 24:859–868. 2005. View Article : Google Scholar : PubMed/NCBI

8. 

Kajita M, Itoh Y, Chiba T, et al: Membrane-type 1 matrix metalloproteinase cleaves CD44 and promotes cell migration. J Cell Biol. 153:893–904. 2001. View Article : Google Scholar : PubMed/NCBI

9. 

Savinov AY, Rozanov DV and Strongin AY: Mechanistic insights into targeting T cell membrane proteinase to promote islet beta-cell rejuvenation in type 1 diabetes. FASEB J. 20:1793–1801. 2006. View Article : Google Scholar : PubMed/NCBI

10. 

Cappuzzo F, Bartolini S and Crinó L: Emerging drugs for non-small cell lung cancer. Expert Opin Emerg Drugs. 8:179–192. 2003. View Article : Google Scholar : PubMed/NCBI

11. 

Ikejiri M, Bernardo MM, Bonfil RD, et al: Potent mechanism-based inhibitors for matrix metalloproteinases. J Biol Chem. 280:33992–34002. 2005. View Article : Google Scholar : PubMed/NCBI

12. 

Rosenblum G, Meroueh SO, Kleifeld O, et al: Structural basis for potent slow binding inhibition of human matrix metalloproteinase-2 (MMP-2). J Biol Chem. 278:27009–27015. 2003. View Article : Google Scholar : PubMed/NCBI

13. 

Annabi B, Lachambre MP, Bousquet-Gagnon N, Page M, Gingras D and Beliveau R: Green tea polyphenol (−)-epigallocatechin 3-gallate inhibits MMP-2 secretion and MT1-MMP-driven migration in glioblastoma cells. Biochim Biophys Acta. 1542:209–220. 2002.

14. 

Cheng XW, Kuzuya M, Kanda S, et al: Epigallocatechin-3-gallate binding to MMP-2 inhibits gelatinolytic activity without influencing the attachment to extracellular matrix proteins but enhances MMP-2 binding to TIMP-2. Arch Biochem Biophys. 415:126–132. 2003. View Article : Google Scholar

15. 

Cheng XW, Kuzuya M, Nakamura K, et al: Mechanisms of the inhibitory effect of epigallocatechin-3-gallate on cultured human vascular smooth muscle cell invasion. Arterioscler Thromb Vasc Biol. 25:1864–1870. 2005. View Article : Google Scholar : PubMed/NCBI

16. 

Dell’Aica I, Donà M, Sartor L, Pezzato E and Garbisa S: (−)Epigallocatechin-3-gallate directly inhibits MT1-MMP activity, leading to accumulation of nonactivated MMP-2 at the cell surface. Lab Invest. 82:1685–1693. 2002.

17. 

Demeule M, Brossard M, Pagé M, Gingras D and Béliveau R: Matrix metalloproteinase inhibition by green tea catechins. Biochim Biophys Acta. 1478:51–60. 2000. View Article : Google Scholar : PubMed/NCBI

18. 

Yamakawa S, Asai T, Uchida T, Matsukawa M, Akizawa T and Oku N: (−)-Epigallocatechin gallate inhibits membrane-type 1 matrix metalloproteinase, MT1-MMP, and tumor angiogenesis. Cancer Lett. 210:47–55. 2004.

19. 

Savinov AY, Wong FS, Stonebraker AC and Chervonsky AV: Presentation of antigen by endothelial cells and chemoattraction are required for homing of insulin-specific CD8+ T cells. J Exp Med. 197:643–656. 2003. View Article : Google Scholar : PubMed/NCBI

20. 

Wong FS, Visintin I, Wen L, Flavell RA and Janeway CA Jr: CD8 T cell clones from young nonobese diabetic (NOD) islets can transfer rapid onset of diabetes in NOD mice in the absence of CD4 cells. J Exp Med. 183:67–76. 1996. View Article : Google Scholar : PubMed/NCBI

21. 

Strongin AY, Collier I, Bannikov G, Marmer BL, Grant GA and Goldberg GI: Mechanism of cell surface activation of 72-kDa type IV collagenase. Isolation of the activated form of the membrane metalloprotease. J Biol Chem. 270:5331–5338. 1995. View Article : Google Scholar : PubMed/NCBI

22. 

Strongin AY, Marmer BL, Grant GA and Goldberg GI: Plasma membrane-dependent activation of the 72-kDa type IV collagenase is prevented by complex formation with TIMP-2. J Biol Chem. 268:14033–14039. 1993.PubMed/NCBI

23. 

Egeblad M and Werb Z: New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer. 2:161–174. 2002. View Article : Google Scholar : PubMed/NCBI

24. 

Li W, Savinov AY, Rozanov DV, et al: Matrix metalloproteinase-26 is associated with estrogen-dependent malignancies and targets alpha1-antitrypsin serpin. Cancer Res. 64:8657–8665. 2004. View Article : Google Scholar : PubMed/NCBI

25. 

Mast AE, Enghild JJ, Nagase H, Suzuki K, Pizzo SV and Salvesen G: Kinetics and physiologic relevance of the inactivation of alpha 1-proteinase inhibitor, alpha 1-antichymotrypsin, and antithrombin III by matrix metalloproteinases-1 (tissue collagenase), -2 (72-kDa gelatinase/type IV collagenase), and -3 (stromelysin). J Biol Chem. 266:15810–15816. 1991.

26. 

Strongin AY: Mislocalization and unconventional functions of cellular MMPs in cancer. Cancer Metastasis Rev. 25:87–98. 2006. View Article : Google Scholar : PubMed/NCBI

27. 

Zhou YP, Madjidi A, Wilson ME, et al: Matrix metalloproteinases contribute to insulin insufficiency in Zucker diabetic fatty rats. Diabetes. 54:2612–2619. 2005. View Article : Google Scholar : PubMed/NCBI

28. 

O’Brien PM, Ortwine DF, Pavlovsky AG, et al: Structure-activity relationships and pharmacokinetic analysis for a series of potent, systemically available biphenylsulfonamide matrix metalloproteinase inhibitors. J Med Chem. 43:156–166. 2000.

29. 

Peterson JT, Hallak H, Johnson L, et al: Matrix metalloproteinase inhibition attenuates left ventricular remodeling and dysfunction in a rat model of progressive heart failure. Circulation. 103:2303–2309. 2001. View Article : Google Scholar

30. 

Savinov AY and Strongin AY: Matrix metalloproteinases, T cell homing and beta-cell mass in type 1 diabetes. Vitam Horm. 80:541–562. 2009. View Article : Google Scholar : PubMed/NCBI

31. 

Chong AS, Shen J, Tao J, et al: Reversal of diabetes in non-obese diabetic mice without spleen cell-derived beta cell regeneration. Science. 311:1774–1775. 2006. View Article : Google Scholar : PubMed/NCBI

32. 

Suri A, Calderon B, Esparza TJ, Frederick K, Bittner P and Unanue ER: Immunological reversal of autoimmune diabetes without hematopoietic replacement of beta cells. Science. 311:1778–1780. 2006. View Article : Google Scholar : PubMed/NCBI

33. 

Nishio J, Gaglia JL, Turvey SE, Campbell C, Benoist C and Mathis D: Islet recovery and reversal of murine type 1 diabetes in the absence of any infused spleen cell contribution. Science. 311:1775–1778. 2006. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Savinov AY and Strongin AY: Targeting the T‑cell membrane type-1 matrix metalloproteinase‑CD44 axis in a transferred type 1 diabetes model in NOD mice. Exp Ther Med 5: 438-442, 2013.
APA
Savinov, A.Y., & Strongin, A.Y. (2013). Targeting the T‑cell membrane type-1 matrix metalloproteinase‑CD44 axis in a transferred type 1 diabetes model in NOD mice. Experimental and Therapeutic Medicine, 5, 438-442. https://doi.org/10.3892/etm.2012.821
MLA
Savinov, A. Y., Strongin, A. Y."Targeting the T‑cell membrane type-1 matrix metalloproteinase‑CD44 axis in a transferred type 1 diabetes model in NOD mice". Experimental and Therapeutic Medicine 5.2 (2013): 438-442.
Chicago
Savinov, A. Y., Strongin, A. Y."Targeting the T‑cell membrane type-1 matrix metalloproteinase‑CD44 axis in a transferred type 1 diabetes model in NOD mice". Experimental and Therapeutic Medicine 5, no. 2 (2013): 438-442. https://doi.org/10.3892/etm.2012.821
Copy and paste a formatted citation
x
Spandidos Publications style
Savinov AY and Strongin AY: Targeting the T‑cell membrane type-1 matrix metalloproteinase‑CD44 axis in a transferred type 1 diabetes model in NOD mice. Exp Ther Med 5: 438-442, 2013.
APA
Savinov, A.Y., & Strongin, A.Y. (2013). Targeting the T‑cell membrane type-1 matrix metalloproteinase‑CD44 axis in a transferred type 1 diabetes model in NOD mice. Experimental and Therapeutic Medicine, 5, 438-442. https://doi.org/10.3892/etm.2012.821
MLA
Savinov, A. Y., Strongin, A. Y."Targeting the T‑cell membrane type-1 matrix metalloproteinase‑CD44 axis in a transferred type 1 diabetes model in NOD mice". Experimental and Therapeutic Medicine 5.2 (2013): 438-442.
Chicago
Savinov, A. Y., Strongin, A. Y."Targeting the T‑cell membrane type-1 matrix metalloproteinase‑CD44 axis in a transferred type 1 diabetes model in NOD mice". Experimental and Therapeutic Medicine 5, no. 2 (2013): 438-442. https://doi.org/10.3892/etm.2012.821
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