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Journal of Biomedicine and Biotechnology
Volume 2011 (2011), Article ID 290874, 7 pages
http://dx.doi.org/10.1155/2011/290874
Review Article

A Transgenic Mouse Model for Studying the Role of the Parathyroid Hormone-Related Protein System in Renal Injury

1Laboratory of Renal Physiology and Experimental Nephrology, Department of Physiology, School of Medicine, Alcalá University, University Campus, 28871 Alcalá de Henares, Spain
2Department of Biochemistry, ‘Principe de Asturias’ University Hospital, University of Alcalá, 28871 Alcalá de Henares, Spain
3Nephrology Department, Puigvert Foundation, 08025 Barcelona, Spain
4Bone and Mineral Metabolism Laboratory, Biomedical Research Institute-Jiménez Díaz, 28040 Madrid, Spain

Received 13 September 2010; Accepted 11 October 2010

Academic Editor: Oreste Gualillo

Copyright © 2011 Ricardo J. Bosch et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. T. J. Martin, J. M. Moseley, and E. D. Williams, “Parathyroid hormone-related protein: hormone and cytokine,” Journal of Endocrinology, vol. 154, supplement, pp. S23–S37, 1997. View at Scopus
  2. W. M. Philbrick, J. J. Wysolmerski, S. Galbraith et al., “Defining the roles of parathyroid hormone-related protein in normal physiology,” Physiological Reviews, vol. 76, no. 1, pp. 127–173, 1996. View at Scopus
  3. F. de Miguel, J. L. Motellón, J. Hurtado, F. J. Jiménez, and P. Esbrit, “Comparison of two immunoradiometric assays for parathyroid hormone-related protein in the evaluation of cancer patients with and without hypercalcemia,” Clinica Chimica Acta, vol. 277, no. 2, pp. 171–180, 1998. View at Publisher · View at Google Scholar · View at Scopus
  4. T. L. Clemens, S. Cormier, A. Eichinger et al., “Parathyroid hormone-related protein and its receptors: nuclear functions and roles in the renal and cardiovascular systems, the placental trophoblasts and the pancreatic islets,” British Journal of Pharmacology, vol. 134, no. 6, pp. 1113–1136, 2001. View at Scopus
  5. T. Massfelder, A. F. Stewart, K. Endlich, N. Soifer, C. Judes, and J.-J. Helwig, “Parathyroid hormone-related protein detection and interaction with NO and cyclic AMP in the renovascular system,” Kidney International, vol. 50, no. 5, pp. 1591–1603, 1996. View at Scopus
  6. T. Yang, S. Hassan, Y. G. Huang, A. M. Smart, J. P. Briggs, and J. B. Schnermann, “Expression of PTHrP, PTH/PTHrP receptor, and Ca2+-sensing receptor mRNAS along the rat nephron,” American Journal of Physiology, vol. 272, no. 6, pp. F751–F758, 1997. View at Scopus
  7. R. J. Bosch, P. Rojo-Linares, G. Torrecillas-Casamayor, M. C. Iglesias-Cruz, D. Rodríguez-Puyol, and M. Rodríguez-Puyol, “Effects of parathyroid hormone-related protein on human mesangial cells in culture,” American Journal of Physiology, vol. 277, no. 6, pp. E990–E995, 1999. View at Scopus
  8. P. Esbrit, S. Santos, A. Ortega et al., “Parathyroid hormone-related protein as a renal regulating factor: from vessels to glomeruli and tubular epithelium,” American Journal of Nephrology, vol. 21, no. 3, pp. 179–184, 2001. View at Publisher · View at Google Scholar · View at Scopus
  9. T. Massfelder, N. Parekh, K. Endlich, C. Saussine, M. Steinhausen, and J.-J. Helwig, “Effect of intrarenally infused parathyroid hormone-related protein on renal blood flow and glomerular filtration rate in the anaesthetized rat,” British Journal of Pharmacology, vol. 118, no. 8, pp. 1995–2000, 1996. View at Scopus
  10. N. Endlich, R. Nobiling, W. Kriz, and K. Endlich, “Expression and signaling of parathyroid hormone-related protein in cultured podocytes,” Experimental Nephrology, vol. 9, no. 6, pp. 436–443, 2001. View at Scopus
  11. N. E. Soifer, S. K. Van Why, M. B. Ganz, M. Kashgarian, N. J. Siegel, and A. F. Stewart, “Expression of parathyroid hormone-related protein in the rat glomerulus and tubule during recovery from renal ischemia,” Journal of Clinical Investigation, vol. 92, no. 6, pp. 2850–2857, 1993. View at Scopus
  12. A. García-Ocaña, F. de Miguel, C. Peñaranda, J. P. Albar, J. L. Sarasa, and P. Esbrit, “Parathyroid hormone-related protein is an autocrine modulator of rabbit proximal tubule cell growth,” Journal of Bone and Mineral Research, vol. 10, no. 12, pp. 1875–1884, 1995. View at Scopus
  13. S. Santos, R. J. Bosch, A. Ortega et al., “Up-regulation of parathyroid hormone-related protein in folic acid-induced acute renal failure,” Kidney International, vol. 60, no. 3, pp. 982–995, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  14. R. Largo, D. Gómez-Garre, S. Santos et al., “Renal expression of parathyroid hormone-related protein (PTHrP) and PTH/PTHrP receptor in a rat model of tubulointerstitial damage,” Kidney International, vol. 55, no. 1, pp. 82–90, 1999. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  15. N. M. Fiaschi-Taesch, S. Santos, V. Reddy et al., “Prevention of acute ischemic renal failure by targeted delivery of growth factors to the proximal tubule in transgenic mice: the efficacy of parathyroid hormone-related protein and hepatocyte growth factor,” Journal of the American Society of Nephrology, vol. 15, no. 1, pp. 112–125, 2004. View at Publisher · View at Google Scholar · View at Scopus
  16. H. D. Humes, E. W. Lake, and S. Liu, “Renal tubule cell repair following acute renal injury,” Mineral and Electrolyte Metabolism, vol. 21, no. 4-5, pp. 353–365, 1995. View at Scopus
  17. S. Vukicevic, V. Basic, D. Rogic et al., “Osteogenic protein-1 (bone morphogenetic protein-7) reduces severity of injury after ischemic acute renal failure in rat,” Journal of Clinical Investigation, vol. 102, no. 1, pp. 202–214, 1998. View at Scopus
  18. K. Matsumoto and T. Nakamura, “Hepatocyte growth factor: renotropic role and potential therapeutics for renal diseases,” Kidney International, vol. 59, no. 6, pp. 2023–2038, 2001. View at Publisher · View at Google Scholar · View at Scopus
  19. G. Gobé, X.-J. Zhang, D. A. Willgoss, E. Schock, N. A. Hogg, and Z. H. Endre, “Relationship between expression of Bcl-2 genes and growth factors in ischemic acute renal failure in the rat,” Journal of the American Society of Nephrology, vol. 11, no. 3, pp. 454–467, 2000. View at Scopus
  20. A. J. Rees, “The role of infiltrating leukocytes in progressive renal disease: implications for therapy,” Nature Clinical Practice Nephrology, vol. 2, no. 7, pp. 348–349, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  21. G. A. Müller, J. Markovic-Lipkovski, J. Frank, and H. P. Rodemann, “The role of interstitial cells in the progression of renal diseases,” Journal of the American Society of Nephrology, vol. 2, no. 10, pp. S198–S205, 1992. View at Scopus
  22. F. Strutz and E. G. Neilson, “New insights into mechanisms of fibrosis in immune renal injury,” Springer Seminars in Immunopathology, vol. 24, no. 4, pp. 459–476, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  23. J. L. Funk, “A role for parathyroid hormone-related protein in the pathogenesis of inflammatory/autoimmune diseases,” International Immunopharmacology, vol. 1, no. 6, pp. 1101–1121, 2001. View at Publisher · View at Google Scholar · View at Scopus
  24. C. Guillén, P. Martínez, A. R. De Gortázar, M. E. Martínez, and P. Esbrit, “Both N- and C-terminal domains of parathyroid hormone-related protein increase interleukin-6 by nuclear factor-κB activation in osteoblastic cells,” The Journal of Biological Chemistry, vol. 277, no. 31, pp. 28109–28117, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  25. J. L. Martín-Ventura, M. Ortego, P. Esbrit, M. A. Hernández-Presa, L. Ortega, and J. Egido, “Possible role of parathyroid hormone-related protein as a proinflammatory cytokine in atherosclerosis,” Stroke, vol. 34, no. 7, pp. 1783–1789, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  26. M. Ishikawa, M. Akishita, K. Kozaki et al., “Expression of parathyroid hormone-related protein in human and experimental atherosclerotic lesions: functional role in arterial intimal thickening,” Atherosclerosis, vol. 152, no. 1, pp. 97–105, 2000. View at Publisher · View at Google Scholar · View at Scopus
  27. T. Nakayama, A. Ohtsuru, H. Enomoto et al., “Coronary atherosclerotic smooth muscle cells overexpress human parathyroid hormone-related peptides,” Biochemical and Biophysical Research Communications, vol. 200, no. 2, pp. 1028–1035, 1994. View at Publisher · View at Google Scholar · View at Scopus
  28. D. Rámila, J. A. Ardura, V. Esteban et al., “Parathyroid hormone-related protein promotes inflammation in the kidney with an obstructed ureter,” Kidney International, vol. 73, no. 7, pp. 835–847, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  29. A. Izquierdo, P. López-Luna, A. Ortega et al., “The parathyroid hormone-related protein system and diabetic nephropathy outcome in streptozotocin-induced diabetes,” Kidney International, vol. 69, no. 12, pp. 2171–2178, 2006. View at Publisher · View at Google Scholar · View at Scopus
  30. G. P. Kaushal, A. G. Basnakian, and S. V. Shah, “Apoptotic pathways in ischemic acute renal failure,” Kidney International, vol. 66, no. 2, pp. 500–506, 2004. View at Publisher · View at Google Scholar · View at Scopus
  31. A. G. Basnakian, G. P. Kaushal, and S. V. Shah, “Apoptotic pathways of oxidative damage to renal tubular epithelial cells,” Antioxidants and Redox Signaling, vol. 4, no. 6, pp. 915–924, 2002. View at Scopus
  32. A. Ortega, D. Rámila, J. A. Ardura et al., “Role of parathyroid hormone-related protein in tubulointerstitial apoptosis and fibrosis after folic acid-induced nephrotoxicity,” Journal of the American Society of Nephrology, vol. 17, no. 6, pp. 1594–1603, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  33. M. L. Gross, E. Ritz, A. Schoof et al., “Comparison of renal morphology in the Streptozotocin and the SHR/N-cp models of diabetes,” Laboratory Investigation, vol. 84, no. 4, pp. 452–464, 2004. View at Publisher · View at Google Scholar · View at PubMed
  34. M. P. O'Donnell, B. L. Kasiske, and W. F. Keane, “Glomerular hemodynamic and structural alterations in experimental diabetes mellitus,” FASEB Journal, vol. 2, no. 8, pp. 2339–2347, 1988.
  35. H.-C. Huang and P. A. Preisig, “G1 kinases and transforming growth factor-β signaling are associated with a growth pattern switch in diabetes-induced renal growth,” Kidney International, vol. 58, no. 1, pp. 162–172, 2000. View at Publisher · View at Google Scholar · View at PubMed
  36. Z.-G. Xu, T.-H. Yoo, D.-R. Ryu et al., “Angiotensin II receptor blocker inhibits p27Kip1 expression in glucose-stimulated podocytes and in diabetic glomeruli,” Kidney International, vol. 67, no. 3, pp. 944–952, 2005. View at Publisher · View at Google Scholar · View at PubMed
  37. T. Pantsulaia, “Role of TGF-beta in pathogenesis of diabetic nephropathy,” Georgian Medical News, no. 131, pp. 13–18, 2006.
  38. M. Romero, A. Ortega, A. Izquierdo, P. López-Luna, and R. J. Bosch, “Parathyroid hormone-related protein induces hypertrophy in podocytes via TGF-β1 and p27Kip1: implications for diabetic nephropathy,” Nephrology Dialysis Transplantation, vol. 25, no. 8, pp. 2447–2457, 2010. View at Publisher · View at Google Scholar · View at PubMed
  39. J. A. Ardura, S. Rayego-Mateos, D. Rámila, M. Ruiz-Ortega, and P. Esbrit, “Parathyroid hormone-related protein promotes epithelial-mesenchymal transition,” Journal of the American Society of Nephrology, vol. 21, no. 2, pp. 237–248, 2010. View at Publisher · View at Google Scholar · View at PubMed
  40. J.-M. Fan, N. G. Yee-Yung, P. A. Hill et al., “Transforming growth factor-β regulates tubular epithelial-myofibroblast transdifferentiation in vitro,” Kidney International, vol. 56, no. 4, pp. 1455–1467, 1999. View at Publisher · View at Google Scholar · View at PubMed
  41. F. Strutz, M. Zeisberg, F. N. Ziyadeh et al., “Role of basic fibroblast growth factor-2 in epithelial-mesenchymal transformation,” Kidney International, vol. 61, no. 5, pp. 1714–1728, 2002. View at Publisher · View at Google Scholar · View at PubMed
  42. W. Lieberthal and J. S. Levine, “Mechanisms of apoptosis and its potential role in renal tubular epithelial cell injury,” American Journal of Physiology, vol. 271, no. 3, pp. R477–R488, 1996.
  43. J. A. Ardura, R. Berruguete, D. Rámila, M. V. Alvarez-Arroyo, and P. Esbrit, “Parathyroid hormone-related protein interacts with vascular endothelial growth factor to promote fibrogenesis in the obstructed mouse kidney,” American Journal of Physiology, vol. 295, no. 2, pp. F415–F425, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  44. Y. Liu, “Epithelial to mesenchymal transition in renal fibrogenesis: pathologic significance, molecular mechanism, and therapeutic intervention,” Journal of the American Society of Nephrology, vol. 15, no. 1, pp. 1–12, 2004. View at Publisher · View at Google Scholar · View at Scopus
  45. R. Kalluri and E. G. Neilson, “Epithelial-mesenchymal transition and its implications for fibrosis,” Journal of Clinical Investigation, vol. 112, no. 12, pp. 1776–1784, 2003. View at Publisher · View at Google Scholar · View at Scopus
  46. F. Strutz and G. A. Müller, “Renal fibrosis and the origin of the renal fibroblast,” Nephrology Dialysis Transplantation, vol. 21, no. 12, pp. 3368–3370, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  47. J. V. Bonventre, “Dedifferentiation and proliferation of surviving epithelial cells in acute renal failure,” Journal of the American Society of Nephrology, vol. 14, no. 1, pp. S55–S61, 2003. View at Scopus
  48. B. Hinz, G. Celetta, J. J. Tomasek, G. Gabbiani, and C. Chaponnier, “Alpha-smooth muscle actin expression upregulates fibroblast contractile activity,” Molecular Biology of the Cell, vol. 12, no. 9, pp. 2730–2741, 2001. View at Scopus
  49. S. Cheng and D. H. Lovett, “Gelatinase A (MMP-2) is necessary and sufficient for renal tubular cell epithelial-mesenchymal transformation,” American Journal of Pathology, vol. 162, no. 6, pp. 1937–1949, 2003. View at Scopus
  50. R. C. Harris and M. Martinez-Maldonado, “Angiotensin II-mediated renal injury,” Mineral and Electrolyte Metabolism, vol. 21, no. 4-5, pp. 328–335, 1995. View at Scopus
  51. J. Egido, “Vasoactive hormones and renal sclerosis,” Kidney International, vol. 49, no. 2, pp. 578–597, 1996. View at Scopus
  52. A. Ortega, D. Rámila, A. Izquierdo et al., “Role of the renin-angiotensin system on the parathyroid hormone-related protein overexpression induced by nephrotoxic acute renal failure in the rat,” Journal of the American Society of Nephrology, vol. 16, no. 4, pp. 939–949, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  53. A. J. Allred, M. C. Chappell, C. M. Ferrario, and D. I. Diz, “Differential actions of renal ischemic injury on the intrarenal angiotensin system,” American Journal of Physiology, vol. 279, no. 4, pp. F636–F645, 2000. View at Scopus
  54. J. Kontogiannis and K. D. Burns, “Role of AT1 angiotensin II receptors in renal ischemic injury,” American Journal of Physiology, vol. 274, no. 1, pp. F79–F90, 1998. View at Scopus
  55. G. W. Long, D. C. Misra, R. Juleff, G. Blossom, P. F. Czako, and J. L. Glover, “Protective effects of enalaprilat against postischemic renal failure,” Journal of Surgical Research, vol. 54, no. 3, pp. 254–257, 1993. View at Publisher · View at Google Scholar · View at Scopus
  56. R. C. Abdulkader, M. M. Yuki, A. C. M. Paiva, and M. Marcondes, “Prolonged inhibition of angiotensin II attenuates glycerol-induced acute renal failure,” Brazilian Journal of Medical and Biological Research, vol. 21, no. 2, pp. 233–239, 1988. View at Scopus
  57. O. Lorenzo, M. Ruiz-Ortega, P. Esbrit et al., “Angiotensin II increases parathyroid hormone-related protein (PTHrP) and the type 1 PTH/PTHrP receptor in the kidney,” Journal of the American Society of Nephrology, vol. 13, no. 6, pp. 1595–1607, 2002. View at Publisher · View at Google Scholar · View at Scopus
  58. C. J. Pirola, H.-M. Wang, A. Kamyar et al., “Angiotensin II regulates parathyroid hormone-related protein expression in cultured rat aortic smooth muscle cells through transcriptional and post- transcriptional mechanisms,” The Journal of Biological Chemistry, vol. 268, no. 3, pp. 1987–1994, 1993. View at Scopus
  59. M. Nodat, T. Katoh, N. Takuwa, M. Kumada, K. Kurokawa, and Y. Takuwa, “Synergistic stimulation of parathyroid hormone-related peptide gene expression by mechanical stretch and angiotensin II in rat aortic smooth muscle cells,” The Journal of Biological Chemistry, vol. 269, no. 27, pp. 17911–17917, 1994. View at Scopus