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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.

Abstract

Parathyroid hormone- (PTH-) related protein (PTHrP) and its receptor, the PTH1 receptor (PTH1R), are widely expressed in the kidney, where PTHrP exerts a modulatory action on renal function. PTHrP is known to be upregulated in several experimental nephropathies such as acute renal failure (ARF), obstructive nephropathy (ON) as well as diabetic nephropathy (DN). In this paper, we will discuss the functional consequences of chronic PTHrP overexpression in the damaged kidney using a transgenic mouse strain overexpressing PTHrP in the renal proximal tubule. In both ARF and ON, PTHrP displays proinflammatory and profibrogenic actions including the induction of epithelia to mesenquima transition. Moreover, PTHrP participates in the mechanisms of renal hypertrophy as well as proteinuria in experimental DN. Angiotensin II (Ang II), a critical factor in the progression of renal injury, appears to be, at least in part, responsible for endogenous PTHrP upregulation in these pathophysiological settings. 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.