A transgenic mouse model for studying the role of the parathyroid hormone-related protein system in renal injury

J Biomed Biotechnol. 2011:2011:290874. doi: 10.1155/2011/290874. Epub 2010 Oct 31.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acute Kidney Injury / drug therapy
  • Acute Kidney Injury / metabolism
  • Angiotensin II / antagonists & inhibitors
  • Animals
  • Disease Models, Animal*
  • Humans
  • Hypertrophy / drug therapy
  • Hypertrophy / metabolism
  • Kidney Diseases / drug therapy
  • Kidney Diseases / metabolism*
  • Mice*
  • Mice, Transgenic
  • Parathyroid Hormone-Related Protein / genetics
  • Parathyroid Hormone-Related Protein / physiology*
  • Proteinuria / drug therapy
  • Proteinuria / metabolism

Substances

  • Parathyroid Hormone-Related Protein
  • Angiotensin II