A transgenic mouse model for studying the role of the parathyroid hormone-related protein system in renal injury.
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.
Laboratory of Renal Physiology and Experimental Nephrology, Department of Physiology, School of Medicine, Alcalá University, University Campus, 28871 Alcalá de Henares, Spain. ricardoj.bosch@uah.es
Ricardo J
RJ
Bosch
Arantxa
A
Ortega
Adriana
A
Izquierdo
Ignacio
I
Arribas
Jordi
J
Bover
Pedro
P
Esbrit
D058186:Acute Kidney Injury / Q000188:drug therapy / Q000378:metabolism; D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D006984:Hypertrophy / Q000188:drug therapy / Q000378:metabolism; D007674:Kidney Diseases / Q000188:drug therapy / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D044162:Parathyroid Hormone-Related Protein / Q000235:genetics / Q000502:physiology*; D011507:Proteinuria / Q000188:drug therapy / Q000378:metabolism
D044162:Parathyroid Hormone-Related Protein; D000804:Angiotensin II