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Journal of Diabetes Research
Volume 2013, Article ID 162846, 6 pages
http://dx.doi.org/10.1155/2013/162846
Review Article

Novel Role of Parathyroid Hormone-Related Protein in the Pathophysiology of the Diabetic Kidney: Evidence from Experimental and Human Diabetic Nephropathy

1Laboratory of Renal Physiology and Experimental Nephrology, Department of Biological Systems/Physiology Unit, University of Alcalá, Alcalá de Henares, Madrid, Spain
2Department of Biomedicine and Biotechnology/Cell Biology Unit, University of Alcalá, Alcalá de Henares, Madrid, Spain
3Nephrology Department, Fundació Puigvert, Barcelona, Spain
4Bone and Mineral Metabolism Laboratory, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Madrid, Spain

Received 17 December 2012; Accepted 4 July 2013

Academic Editor: Bernard Portha

Copyright © 2013 Montserrat Romero 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.

Abstract

Parathyroid hormone-related protein (PTHrP) and its receptor type 1 (PTH1R) are extensively expressed in the kidney, where they are able to modulate renal function. Renal PTHrP is known to be overexpressed in acute renal injury. Recently, we hypothesized that PTHrP involvement in the mechanisms of renal injury might not be limited to conditions with predominant damage of the renal tubulointerstitium and might be extended to glomerular diseases, such as diabetic nephropathy (DN). In experimental DN, the overexpression of both PTHrP and the PTH1R contributes to the development of renal hypertrophy as well as proteinuria. More recent data have shown, for the first time, that PTHrP is upregulated in the kidney from patients with DN. Collectively, animal and human studies have shown that PTHrP acts as an important mediator of diabetic renal cell hypertrophy by a mechanism which involves the modulation of cell cycle regulatory proteins and TGF-β1. Furthermore, angiotensin II (Ang II), a critical factor in the progression of renal injury, appears to be responsible for PTHrP upregulation in these conditions. These findings provide novel insights into the well-known protective effects of Ang II antagonists in renal diseases, paving the way for new therapeutic approaches.