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Disease and gender-specific dysregulation of NGAL and MMP-9 in type 1 diabetes mellitus

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Abstract

Neutrophil gelatinase-associated lipocalin (NGAL), a biomarker of renal injury, can bind matrix metalloproteinase-9 (MMP-9) and inhibit its degradation, thereby sustaining MMP-9 proteolytic activity. MMP-9 is produced by renal podocytes, and podocyte MMP production can be modified by high ambient glucose levels. Moreover, dysregulation of MMP-9 activity, gene expression, or urine concentrations has been demonstrated in T2DM-associated nephropathy and in non-diabetic proteinuric renal diseases. Our objective was to determine whether NGAL/MMP-9 dysregulation might contribute to or serve as a biomarker of diabetic nephropathy in type 1 DM (T1DM). Plasma MMP-9, and urine NGAL and MMP-9 concentrations were measured in 121 T1DM and 55 control subjects and examined relative to indicators of glycemia, renal function, and degree of albuminuria. T1DM was associated with a significant increase in urinary excretion of both NGAL and MMP-9, and urine NGAL:Cr (NGAL corrected to urine creatinine) and urine MMP-9:Cr concentrations were highly correlated with each other. Both were also positively correlated with measurements of glycemic control and with albuminuria. Plasma MMP-9, urine MMP-9, and urine NGAL concentrations were significantly higher in females compared to males, and urine MMP-9:Cr concentrations displayed a menstrual cycle specific pattern. Increased urinary excretion of NGAL and MMP-9 supports a role for NGAL/MMP-9 dysregulation in renal dysfunction; moreover, gender-specific differences could support a gender contribution to pathological mechanisms or susceptibility for the development of renal complications in diabetes mellitus.

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References

  1. R. Visse, H. Nagase, Circ. Res. 92, 827–839 (2003)

    Article  CAS  PubMed  Google Scholar 

  2. H. Nagase, R. Visse, G. Murphy, Cardiovasc. Res. 69, 562–573 (2006)

    Article  CAS  PubMed  Google Scholar 

  3. Z. Werb, Cell 91, 439–442 (1997)

    Article  CAS  PubMed  Google Scholar 

  4. A.J. Barrett, Methods Enzymol. 80 Pt C, 737–754 (1981)

    Article  CAS  PubMed  Google Scholar 

  5. M.P. Herman, G.K. Sukhova, W. Kisiel, D. Foster, M.R. Kehry et al., J. Clin. Invest. 107, 1117–1126 (2001)

    Article  CAS  PubMed  Google Scholar 

  6. G. Derosa, I. Ferrari, A. D’Angelo, C. Tinelli, S.A. Salvadeo et al., Endothelium 15, 219–224 (2008)

    Article  CAS  PubMed  Google Scholar 

  7. B. Glowinska-Olszewska, M. Urban, Metabolism 56, 799–805 (2007)

    Article  CAS  PubMed  Google Scholar 

  8. F.M. Goncalves, A.L. Jacob-Ferreira, V.A. Gomes, A. Casella-Filho, A.C. Chagas et al., Clin. Chim. Acta 403, 173–177 (2009)

    Article  CAS  PubMed  Google Scholar 

  9. G. Derosa, A. D’Angelo, C. Tinelli, E. Devangelio, A. Consoli et al., Diabetes Metab. 33, 129–134 (2007)

    Article  CAS  PubMed  Google Scholar 

  10. G. Derosa, A.F. Cicero, F. Scalise, M.A. Avanzini, C. Tinelli et al., Endothelium 14, 45–51 (2007)

    Article  CAS  PubMed  Google Scholar 

  11. S.S. Signorelli, G. Malaponte, M. Libra, L. Di Pino, G. Celotta et al., Vasc. Med. 10, 1–6 (2005)

    Article  PubMed  Google Scholar 

  12. S. Jacqueminet, O. Ben Abdesselam, M.J. Chapman, N. Nicolay, M.J. Foglietti et al., Clin. Chim. Acta 367, 103–107 (2006)

    Article  CAS  PubMed  Google Scholar 

  13. A.K. Death, E.J. Fisher, K.C. McGrath, D.K. Yue, Atherosclerosis 168, 263–269 (2003)

    Article  CAS  PubMed  Google Scholar 

  14. G. Qing-Hua, L. Ju-Ming, P. Chang-Yu, L. Zhao-Hui, Z. Xiao-Man, M. Yi-Ming, J. Diabetes Complications 22, 408–412 (2008)

    Article  PubMed  Google Scholar 

  15. K. Tashiro, I. Koyanagi, I. Ohara, T. Ito, A. Saitoh et al., J. Clin. Lab. Anal. 18, 206–210 (2004)

    Article  CAS  PubMed  Google Scholar 

  16. A. Lauhio, T. Sorsa, R. Srinivas, M. Stenman, T. Tervahartiala et al., Ann. Med. 40, 312–320 (2008)

    Article  CAS  PubMed  Google Scholar 

  17. S. Liu, Y. Li, H. Zhao, D. Chen, Q. Huang et al., Mol. Cell. Biochem. 284, 9–17 (2006)

    Article  CAS  PubMed  Google Scholar 

  18. T. Kuroda, Y. Yoshida, J. Kamiie, P. Kovalenko, M. Nameta et al., Clin. Exp. Nephrol. 8, 206–215 (2004)

    Article  CAS  PubMed  Google Scholar 

  19. T.S. Ahuja, A. Gopalani, P. Davies, H. Ahuja, Nephron Clin. Pract. 95, c100–c104 (2003)

    Article  CAS  PubMed  Google Scholar 

  20. P. Devarajan, Scand. J. Clin. Lab. Invest. Suppl. 241, 89–94 (2008)

    Article  PubMed  Google Scholar 

  21. Y.H. Yang, X.J. He, S.R. Chen, L. Wang, E.M. Li, L.Y. Xu, Endocrine 36, 45–51 (2009)

    Article  PubMed  Google Scholar 

  22. D. Bolignano, A. Lacquaniti, G. Coppolino, V. Donato, M.R. Fazio et al., Kidney Blood Press. Res. 32, 91–98 (2009)

    Article  CAS  PubMed  Google Scholar 

  23. N. Malla, S. Sjoli, J.O. Winberg, E. Hadler-Olsen, L. Uhlin-Hansen, Connect. Tissue Res. 49, 180–184 (2008)

    Article  CAS  PubMed  Google Scholar 

  24. N. Fiotti, N. Altamura, M. Moretti, S. Wassermann, S. Zacchigna et al., Cardiovasc. Drugs Ther. 23, 153–159 (2009)

    Article  CAS  PubMed  Google Scholar 

  25. H. Kramer, M.E. Molitch, Diabetes Care 28, 1813–1816 (2005)

    Article  PubMed  Google Scholar 

  26. American Diabetes Association, Diabetes Care 26, 94S–98S (2003)

    Google Scholar 

  27. K.M. Thrailkill, R.C. Bunn, C.S. Moreau, G.E. Cockrell, P.M. Simpson et al., Diabetes Care 30, 2321–2326 (2007)

    Article  CAS  PubMed  Google Scholar 

  28. K.M. Thrailkill, C.S. Moreau, G. Cockrell, P. Simpson, R. Goel et al., Clin. Chem. Lab. Med. 43, 1392–1399 (2005)

    Article  CAS  PubMed  Google Scholar 

  29. American Diabetes Association, Diabetes Care 32(Suppl 1), S13–S61 (2009)

    Google Scholar 

  30. C.A. Paris, G. Imperatore, G. Klingensmith, D. Petitti, B. Rodriguez et al., J. Pediatr. 155, 183–189.e1 (2009)

    Article  PubMed  Google Scholar 

  31. K.M. Thrailkill, T. Nimmo, R.C. Bunn, G.E. Cockrell, C.S. Moreau et al., Diabetes Care 32, 1266–1268 (2009)

    Article  CAS  PubMed  Google Scholar 

  32. H. Birn, Am. J. Physiol. Renal Physiol. 291, F22–F36 (2006)

    Article  CAS  PubMed  Google Scholar 

  33. V. Hvidberg, C. Jacobsen, R.K. Strong, J.B. Cowland, S.K. Moestrup, N. Borregaard, FEBS Lett. 579, 773–777 (2005)

    Article  CAS  PubMed  Google Scholar 

  34. P.E. Van den Steen, I. Van Aelst, V. Hvidberg, H. Piccard, P. Fiten et al., J. Biol. Chem. 281, 18626–18637 (2006)

    Article  PubMed  Google Scholar 

  35. L. Yan, N. Borregaard, L. Kjeldsen, M.A. Moses, J. Biol. Chem. 276, 37258–37265 (2001)

    Article  CAS  PubMed  Google Scholar 

  36. N. Engl. J. Med. 329, 977–986 (1993)

  37. H.L. Huang, S.T. Chu, Y.H. Chen, J. Endocrinol. 162, 11–19 (1999)

    Article  CAS  PubMed  Google Scholar 

  38. P. Seth, D. Porter, J. Lahti-Domenici, Y. Geng, A. Richardson, K. Polyak, Cancer Res. 62, 4540–4544 (2002)

    CAS  PubMed  Google Scholar 

  39. R.W. Mankhey, C.C. Wells, F. Bhatti, C. Maric, Am. J. Physiol. Regul. Integr. Comp. Physiol. 292, R769–R777 (2007)

    CAS  PubMed  Google Scholar 

  40. D.Z. Cherney, E.B. Sochett, J.A. Miller, Kidney Int. 68, 1722–1728 (2005)

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors appreciate the critical review of this manuscript provided by Dr. Lindsey Clark. This work was supported by grants from the National Institutes of Health to KMT (R01-DK62999), to the UAMS General Clinical Research Center (M01 RR14288) and to the Arkansas Children’s Hospital Research Institute (C06RR16517).

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Authors and Affiliations

  1. Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, 72202, USA

    Kathryn M. Thrailkill, Cynthia S. Moreau, Gael E. Cockrell, Chan-Hee Jo, Robert C. Bunn, Alba E. Morales-Pozzo, Charles K. Lumpkin & John L. Fowlkes

  2. Arkansas Children’s Hospital Research Institute, #1 Children’s Way; Slot 512-6, Little Rock, AR, 72202, USA

    Kathryn M. Thrailkill, Cynthia S. Moreau, Gael E. Cockrell, Robert C. Bunn, Alba E. Morales-Pozzo, Charles K. Lumpkin & John L. Fowlkes

  3. Arkansas Children’s Hospital Research Institute, #1 Children’s Way; Slot 512-43, Little Rock, AR, 72202, USA

    Chan-Hee Jo

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  1. Kathryn M. Thrailkill
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  2. Cynthia S. Moreau
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Correspondence to Kathryn M. Thrailkill.

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Thrailkill, K.M., Moreau, C.S., Cockrell, G.E. et al. Disease and gender-specific dysregulation of NGAL and MMP-9 in type 1 diabetes mellitus. Endocr 37, 336–343 (2010). https://doi.org/10.1007/s12020-010-9308-6

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  • DOI: https://doi.org/10.1007/s12020-010-9308-6

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