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Angiotensin II- and glucose-stimulated extracellular matrix production: mediation by the insulin-like growth factor (IGF) axis in a murine mesangial cell line

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Abstract

In diabetic nephropathy, glomerular mesangial cells exhibit aberrant anabolic activity that includes excessive production of extracellular matrix (ECM) proteins, leading to crowding of filtration surface areas and possible renal failure. In the present study, a murine mesangial cell line (MES-13 cells) was studied to determine the roles of the renin-angiotensin system (RAS) and the insulin-like growth factor (IGF) axis in the anabolic response to elevated glucose levels. Culture of MES-13 cells in medium containing supra-physiological glucose concentrations (>5.5 mmol/l) resulted in increased production of ECM proteins including laminin, fibronectin, and heparan sulfate proteoglycan with concurrent increases in IGF-binding protein (IGFBP)-2 production. These responses were blocked by the angiotensin receptor antagonists saralasin and losartan, while exogenous angiotensin II (Ang II) treatment directly stimulated increases in ECM and IGFBP-2. In all experiments, IGFBP-2 levels were correlated with anabolic activity implicating IGFBP-2 as a possible mediator in cellular responses to high glucose and Ang II. Such mediation appears to involve IGFBP-2 modulation of IGF-I signaling, since all responses to high glucose or Ang II were blocked by immuno-neutralization of IGF-I. These data suggest alterations in the IGF axis as key mechanisms underlying nephropathic responses of mesangial cells to Ang II and high glucose.

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References

  1. M. Steffes, et al., Diabetes 38, 1077–1081 (1989)

    Article  CAS  PubMed  Google Scholar 

  2. M.S. Simonson, Kidney Int. 71, 846–854 (2007)

    Article  CAS  PubMed  Google Scholar 

  3. S.H. Ayo, et al., Am. J. Physiol. 260, F185–F191 (1991)

    CAS  PubMed  Google Scholar 

  4. N.A. Wahab, K. Harper, R.M. Mason, Biochem. J. 316, 985–992 (1996)

    CAS  PubMed  Google Scholar 

  5. R. Lehmann, E.D. Schleicher, Clin. Chim. Acta 297, 135–144 (2000)

    Article  CAS  PubMed  Google Scholar 

  6. R.M. Mason, N.A. Abdel Wahab, J. Am. Soc. Nephrol. 14, 1358–1373 (2003)

    Article  CAS  PubMed  Google Scholar 

  7. J.H. Oh, et al., Kidney Int. 54, 1872–1878 (1998)

    Article  CAS  PubMed  Google Scholar 

  8. M. Kitamura, et al., Biochem. Biophys. Res. Commun. 185, 1048–1054 (1992)

    Article  CAS  PubMed  Google Scholar 

  9. F.P. Schena, L. Gesualdo, J. Am. Soc. Nephrol. 16, S30–S33 (2005)

    Article  CAS  PubMed  Google Scholar 

  10. D. Leehey, et al., Kidney Int. Suppl. 77, S93–98 (2000)

    Article  CAS  PubMed  Google Scholar 

  11. W.A. Hsueh, et al., Adv. Exp. Med. Biol. 377, 217–223 (1995)

    CAS  PubMed  Google Scholar 

  12. S.A. Mezzano, M. Ruiz-Ortega, J. Egido, Hypertension 38, 635–638 (2001)

    Article  CAS  PubMed  Google Scholar 

  13. R. Singh, et al., Diabetes 48, 2066–2073 (1999)

    Article  CAS  PubMed  Google Scholar 

  14. R. Singh, et al., J. Am. Soc. Nephrol. 14, 873–880 (2003)

    Article  CAS  PubMed  Google Scholar 

  15. K. Ikehara, et al., Diabetes Res. Clin. Pract. 59, 25–30 (2003)

    Article  CAS  PubMed  Google Scholar 

  16. D.B. Vidotti, Am. J. Physiol. Renal Physiol. 286, F1039–F1045 (2004)

    Article  CAS  PubMed  Google Scholar 

  17. D. Landau, et al., Endocrinology 136, 1835–1842 (1995)

    Article  CAS  PubMed  Google Scholar 

  18. G. Pugliese, et al., Diabetologia 39, 775–784 (1996)

    Article  CAS  PubMed  Google Scholar 

  19. V. Cingel-Ristic, A. Flyvbjerg, S.L. Drop, Growth Horm. IGF Res. 14, 418–430 (2004)

    CAS  PubMed  Google Scholar 

  20. A. Flyvbjerg, et al., Metabolism 44, 67–71 (1995)

    Article  CAS  PubMed  Google Scholar 

  21. A. Flyvbjerg, et al., Curr. Pharm. Des. 10, 3385–3394 (2004)

    Article  CAS  PubMed  Google Scholar 

  22. T.L. Vasylyeva, R.J. Ferry Jr., Diabetes Res. Clin. Pract. 76, 177–186 (2006)

    Article  PubMed  Google Scholar 

  23. Y. Liu, Kidney Int. 69, 213–217 (2006)

    Article  CAS  PubMed  Google Scholar 

  24. S. Kagami, et al., J. Clin. Invest. 93, 2431–2437 (1994)

    Article  CAS  PubMed  Google Scholar 

  25. S. Chen, B. Jim, F.N. Ziyadeh, Semin. Nephrol. 23, 532–543 (2003)

    Article  CAS  PubMed  Google Scholar 

  26. F.N. Ziyadeh, J. Am. Soc. Nephrol. 15, S55–S57 (2004)

    Article  CAS  PubMed  Google Scholar 

  27. R. Ardaillou, et al., J. Am. Soc. Nephrol. 10, S40–S46 (1999)

    CAS  PubMed  Google Scholar 

  28. S. Kim, H. Iwao, Pharmacol. Rev. 52, 11–34 (2000)

    CAS  PubMed  Google Scholar 

  29. F. Amiri, et al., Kidney Int. 61, 1605–1616 (2002)

    Article  CAS  PubMed  Google Scholar 

  30. G. Wolf, Kidney Int. 70, 1914–1919 (2006)

    CAS  PubMed  Google Scholar 

  31. R. Rabkin, F. Schaefer, Growth Horm. IGF Res. 14, 270–276 (2004)

    Article  CAS  PubMed  Google Scholar 

  32. H.J. Han, C.W. Kang, S.H. Park, Clin. Exp. Pharmacol. Physiol. 33, 1172–1179 (2006)

    Article  CAS  PubMed  Google Scholar 

  33. A. Flyvbjerg, Diabetologia 43, 1205–1223 (2000)

    Article  CAS  PubMed  Google Scholar 

  34. M.J. Horney, et al., Am. J. Physiol. Renal Physiol. 274, F1045–F1053 (1998)

    CAS  Google Scholar 

  35. W. Song, et al., Diabetes 49(suppl.), A379 (2000)

    Google Scholar 

  36. J. Haylor, et al., J. Am. Soc. Nephrol. 11, 2027–2035 (2000)

    CAS  PubMed  Google Scholar 

  37. Y. Jiang, et al., Mol. Cell Biochem. 278, 165–175 (2005)

    Article  CAS  PubMed  Google Scholar 

  38. S.M. Feld, et al., Kidney Int. 48, 45–51 (1995)

    Article  CAS  PubMed  Google Scholar 

  39. B.D. Schreiber, M.L. Hughes, G.C. Groggel, Clin. Nephrol. 43, 368–374 (1995)

    CAS  PubMed  Google Scholar 

  40. J.L. Gooch, et al., J. Biol. Chem. 276, 42492–42500 (2001)

    Article  CAS  PubMed  Google Scholar 

  41. B.P. Kang, et al., Am. J. Physiol. Renal Physiol. 28, F1013–F1024 (2003)

    Google Scholar 

  42. S. Yang, et al., Am. J. Physiol. Renal Physiol. 289, F1144–F1152 (2005)

    Article  CAS  PubMed  Google Scholar 

  43. K.M. Kelley, L.D. Nonoshita, R.G. Rosenfeld. in Proceedings 77th Annual Meeting of the Endocrine Society (vol P.170) (1995)

  44. I.S. Park, et al., Am. J. Kidney Dis. 32, 1000–1010 (1998)

    Article  CAS  PubMed  Google Scholar 

  45. V. Cingel-Ristic, et al., Exp. Biol. Med. 230, 135–143 (2005)

    CAS  Google Scholar 

  46. K.M. Kelley, et al., J. Endocrinol. 175, 3–18 (2002)

    Article  CAS  PubMed  Google Scholar 

  47. S.M. Firth, R.C. Baxter, Endocrine Rev. 23, 824–854 (2002)

    Article  CAS  Google Scholar 

  48. P. Grellier, et al., Kidney Int. 49, 1071–1078 (1996)

    Article  CAS  PubMed  Google Scholar 

  49. A. Fornoni, et al., Endocrinology 147, 3547–3554 (2006)

    Article  CAS  PubMed  Google Scholar 

  50. M. Burnier, Circulation. 103, 904–912 (2001)

    CAS  PubMed  Google Scholar 

  51. M.C. Andrade, et al., J. Hypertens. 16, 2063–2074 (1998)

    Article  CAS  PubMed  Google Scholar 

  52. A.Q. Andrade, et al., Braz. J. Med. Biol. Res. 35, 17–24 (2002)

    CAS  PubMed  Google Scholar 

  53. G. Wolf, U. Haberstroh, E.G. Neilson, Am. J. Pathol. 140, 95–107 (1992)

    CAS  PubMed  Google Scholar 

  54. B.D. Rodgers, R.M. Bautista, C.S. Nicoll, Proc. Soc. Exp. Biol. Med. 210, 234–241 (1995)

    Google Scholar 

  55. A. Akinci, et al., Metabolism 49, 626–633 (2000)

    Article  CAS  PubMed  Google Scholar 

  56. M.C. Slootweg, et al., Endocrinology 136, 4210–4217 (1995)

    Article  CAS  PubMed  Google Scholar 

  57. A. Hoeflich, et al., FEBS Lett. 434, 329–334 (1998)

    Article  Google Scholar 

  58. E. Wolf, et al., Pediatr. Nephrol. 14, 572–578 (2000)

    Article  CAS  PubMed  Google Scholar 

  59. C.A. Conover, S. Khosla, Growth Horm. IGF Res. 13, 328–335 (2003)

    Article  CAS  PubMed  Google Scholar 

  60. A. Blackburn, et al., Eur. J. Endocrinol. 137, 701–708 (1997)

    Article  CAS  PubMed  Google Scholar 

  61. R. Novosyadlyy, et al., J. Cell Physiol. 199, 388–398 (2004)

    Article  CAS  PubMed  Google Scholar 

  62. K. MacKay, et al., Kidney Int. 33, 677–684 (1988)

    Article  CAS  PubMed  Google Scholar 

  63. K.M. Kelley, et al., Am. J. Physiol. 276, R1164–R1171 (1999)

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Merck & Co., Inc. for generously providing losartan. They also acknowledge funding by CSULB University Scholarly and Creative Activities Awards and Howard Hughes Medical Institute Grant #52002663.

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Author notes

  1. Lori K. Davis

    Present address: Hawaii Institute of Marine Biology, University of Hawaii, Kaneohe, HI, 96744, USA

Authors and Affiliations

  1. Endocrinology Laboratory, Department of Biological Sciences, California State University, Long Beach, Long Beach, CA, 90840, USA

    Lori K. Davis & Kevin M. Kelley

  2. Department of Animal Sciences, Washington State University, Pullman, WA, 99164, USA

    Buel D. Rodgers

Authors
  1. Lori K. Davis
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  2. Buel D. Rodgers
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  3. Kevin M. Kelley
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Correspondence to Kevin M. Kelley.

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Davis, L.K., Rodgers, B.D. & Kelley, K.M. Angiotensin II- and glucose-stimulated extracellular matrix production: mediation by the insulin-like growth factor (IGF) axis in a murine mesangial cell line. Endocr 33, 32–39 (2008). https://doi.org/10.1007/s12020-008-9055-0

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