Up-regulation of parathyroid hormone-related protein in folic acid-induced acute renal failure

Abstract

Renal PTHrP was rapidly and transiently increased in rats with folic acid-induced acute renal failure, featuring as an early response gene. In addition, changes in ACE and Ang II expression were also found in these animals. PTHrP induces a mitogenic response in folic acid-damaged renal tubular cells both in vivo and in vitro. Our results support the notion that PTHrP up-regulation participates in the regenerative process in this model of acute renal failure and is a common event associated with the mechanisms of renal injury and repair.

Leukemia Inhibitory Factor Is Involved in Tubular Regeneration after Experimental Acute Renal Failure

“…Many genes have been reported to be upregulated after tubular injury. Egr-1 (28), c-fos (28), c-myc (29), and the genes encoding heat shock protein-70 (30) and parathyroid hormonerelated protein (PTHrP) (31) have been shown to be upregulated in the very early phase after injury. Their upregulation was detected as early as within a few hours and returned to baseline within 1 d. These are considered the early response genes to renal injury.…”

Parathyroid Hormone-Related Protein as a Mediator of Renal Damage: New Evidence from Experimental as well as Human Nephropathies

“…From then on, the majority of investigations have studied experimental nephropathies characterized by tubular affectation (Fiaschi-Taesch et al, 2004;Largo et al, 1999;Lorenzo et al, 2002;Ortega et al, 2005;Santos et al, 2001). Ischemic and toxic injury to renal tubular epithelial cells can cause both acute and chronic renal failure depending on the intensity of and exposure time to the damage (Humes et al, 1995;Lieberthal & Levine, 1996).…”

“…Several growth factors and cytokines, acting in an autocrine and paracrine manner, appear to participate in the repair process of the tubular epithelium in this setting (Fiaschi-Taesch et al, 2004;Gobe et al, 2000;Humes et al, 1995;Matsumoto & Nakamura, 2001;Vukicevic et al, 1998). The mitogenic features of PTHrP and its early overexpression after renal injury in experimental models of acute renal failure (ARF), induced by either ischemia or nephrotoxins, initially suggested that PTHrP could participate in the regenerative process after ARI (Santos et al, 2001;Soifer et al, 1993). However, this putative role of PTHrP in the acutely damaged kidney was intriguing, since the PTH1R gene was found to be rapidly downregulated following ARI (Santos et al, 2001;Soifer et al, 1993).…”

“…The mitogenic features of PTHrP and its early overexpression after renal injury in experimental models of acute renal failure (ARF), induced by either ischemia or nephrotoxins, initially suggested that PTHrP could participate in the regenerative process after ARI (Santos et al, 2001;Soifer et al, 1993). However, this putative role of PTHrP in the acutely damaged kidney was intriguing, since the PTH1R gene was found to be rapidly downregulated following ARI (Santos et al, 2001;Soifer et al, 1993). This is in sharp contrast to other well characterized renal mitogens, such as epidermal growth factor (EGF) and hepatocyte growth factor (HGF), whose receptors are upregulated after ARI (Humes et al, 1995;Matsumoto & Nakamura, 2001).…”

“…At present, it is well known that PTHrP is a widespread factor in normal tissues, including kidney, where it has autocrine/paracrine/intracrine actions through PTH/PTHrP type 1 receptor (PTH1R) (Clemens et al, 2001). Renal PTHrP overexpression is a common event in several acute as well as chronic nephropathies (Fiaschi-Taesch et al, 2004;Izquierdo et al, 2006;Largo et al, 1999;Lorenzo et al, 2002;Rámila et al, 2008;Santos et al, 2001). During the last years, studies to define the physiopathological role of PTHrP in the renal context have been carried out, using experimental models of tubulointerstitial or glomerular damage.…”