title: Novel role of parathyroid hormone-related protein in the pathophysiology of the diabetic kidney: evidence from experimental and human diabetic nephropathy.
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- β 1. 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.
authors.affiliation: Laboratory of Renal Physiology and Experimental Nephrology, Department of Biological Systems/Physiology Unit, University of Alcalá, Alcalá de Henares, Madrid, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Romero
authors.forename: Arantxa
authors.initials: A
authors.lastname: Ortega
authors.forename: Nuria
authors.initials: N
authors.lastname: Olea
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Arenas
authors.forename: Adriana
authors.initials: A
authors.lastname: Izquierdo
authors.forename: Jordi
authors.initials: J
authors.lastname: Bover
authors.forename: Pedro
authors.initials: P
authors.lastname: Esbrit
authors.forename: Ricardo J
authors.initials: RJ
authors.lastname: Bosch
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000209:etiology* / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism*; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000378:metabolism
chemical_list: D044162:Parathyroid Hormone-Related Protein; D044168:Receptor, Parathyroid Hormone, Type 1