Role of the Renin-Angiotensin System on the Parathyroid Hormone–Related Protein Overexpression Induced by Nephrotoxic Acute Renal Failure in the Rat

Ortega, Arantxa; Rámila, David; Izquierdo, Alberto Galindo; González, L.; Barat, A.; Gazapo, Rosa; Bosch, Ricardo J.; Esbrit, Pedro

doi:10.1681/asn.2004040328

Cited by 44 publications

(55 citation statements)

References 31 publications

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“…Interestingly, a significant correlation between PTHrP overexpression and tubular damage and fibrosis was observed in the rat kidney after systemic Ang II infusion (Lorenzo et al, 2002). Furthermore, in nephrotoxic ARI, the improvement of renal function by Ang II antagonists was associated with inhibition of PTHrP overexpression (Ortega et al, 2005). Collectively, current data suggest that: 1) Ang II is a likely candidate responsible for PTHrP overexpression; and 2) PTHrP might contribute to the deleterious effects of Ang II, in the damaged kidney.…”

Section: Interaction Between Pthrp and Angiotensin II In The Damaged mentioning

confidence: 59%

“…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).…”

Section: Pthrp In Acute Renal Injurymentioning

confidence: 99%

“…The hypothetical beneficial effects of PTHrP as a mitogen in ARI was further questioned when considering that targeted delivery of PTHrP to the proximal tubule in mice failed to provide protection against renal ischemia or folic acid injury (Fiaschi-Taesch et al, 2004). Moreover, experimental data using the latter model in rats showed that pretreatment with Ang II blockers abolished the PTHrP upregulation but not tubular hyperplasia (Ortega et al, 2005). Thus, current evidence makes it unlikely that PTHrP plays a significant role in the regenerative process after ARI.…”

Section: Pthrp In Acute Renal Injurymentioning

confidence: 99%

“…In fact, the main agonist of this system, Ang II, can be envisioned as a growth factor which can promote the progression of kidney damage (Mezzano et al, 2001;Ruiz-Ortega & Egido, 1997). Activation of components of the renin-angiotensin system, including Ang II, locally in the kidney, has been shown to occur early in various experimental models of ARI, e.g., folic acid-induced nephrotoxicity or ischemia/reperfusion (Allred et al, 2000;Kontogiannis & Burns, 1998;Ortega et al, 2005;Santos et al, 2001). Moreover, Ang II antagonists exert beneficial effects on renal function in these models (Abdulkader et al, 1998;Long et al, 1993;Ortega et al, 2005).…”

Section: Interaction Between Pthrp and Angiotensin II In The Damaged mentioning

confidence: 99%

“…Activation of components of the renin-angiotensin system, including Ang II, locally in the kidney, has been shown to occur early in various experimental models of ARI, e.g., folic acid-induced nephrotoxicity or ischemia/reperfusion (Allred et al, 2000;Kontogiannis & Burns, 1998;Ortega et al, 2005;Santos et al, 2001). Moreover, Ang II antagonists exert beneficial effects on renal function in these models (Abdulkader et al, 1998;Long et al, 1993;Ortega et al, 2005). Recent data strongly suggest that PTHrP might be involved in the mechanisms related to Ang II-induced renal injury.…”

Section: Interaction Between Pthrp and Angiotensin II In The Damaged mentioning

confidence: 99%

See 4 more Smart Citations

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

Bosch¹,

Arenas²,

Romero³

et al. 2012

Chronic Kidney Disease and Renal Transplantation

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Section: Interaction Between Pthrp and Angiotensin II In The Damaged mentioning

confidence: 59%

Section: Pthrp In Acute Renal Injurymentioning

confidence: 99%

Section: Pthrp In Acute Renal Injurymentioning

confidence: 99%

Section: Interaction Between Pthrp and Angiotensin II In The Damaged mentioning

confidence: 99%

Section: Interaction Between Pthrp and Angiotensin II In The Damaged mentioning

confidence: 99%

See 3 more Smart Citations

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

Bosch¹,

Arenas²,

Romero³

et al. 2012

Chronic Kidney Disease and Renal Transplantation

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Modeled gravitational unloading induced downregulation of endothelin‐1 in human endothelial cells

Infanger

Ulbrich

Baatout

et al. 2007

J of Cellular Biochemistry

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Many space missions have shown that prolonged space flights may increase the risk of cardiovascular problems. Using a three-dimensional clinostat, we investigated human endothelial EA.hy926 cells up to 10 days under conditions of simulated microgravity (microg) to distinguish transient from long-term effects of microg and 1g. Maximum expression of all selected genes occurred after 10 min of clinorotation. Gene expression (osteopontin, Fas, TGF-beta(1)) declined to slightly upregulated levels or rose again (caspase-3) after the fourth day of clinorotation. Caspase-3, Bax, and Bcl-2 protein content was enhanced for 10 days of microgravity. In addition, long-term accumulation of collagen type I and III and alterations of the cytoskeletal alpha- and beta-tubulins and F-actin were detectable. A significantly reduced release of soluble factors in simulated microgravity was measured for brain-derived neurotrophic factor, tissue factor, vascular endothelial growth factor (VEGF), and interestingly for endothelin-1, which is important in keeping cardiovascular balances. The gene expression of endothelin-1 was suppressed under microg conditions at days 7 and 10. Alterations of the vascular endothelium together with a decreased release of endothelin-1 may entail post-flight health hazards for astronauts.

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Parathyroid hormone‐related protein is a hypertrophy factor for human mesangial cells: Implications for diabetic nephropathy

Ortega

Romero

Izquierdo

et al. 2012

Journal Cellular Physiology

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Hypertrophy of human mesangial cells (HMC) is among the earliest characteristics in patients with diabetic nephropathy (DN). Recently, we observed the upregulation of parathyroid hormone (PTH)-related protein (PTHrP) in experimental DN, associated with renal hypertrophy. Herein, we first examined whether PTHrP was overexpressed in human DN, and next assessed the putative role of this protein on high glucose (HG)-induced HMC hypertrophy. As previously found in mice, kidneys from diabetic patients showed an increased tubular and glomerular immunostaining for PTHrP. In HMC, HG medium increased PTHrP protein expression associated with the development of hypertrophy as assessed by cell protein content. This effect was also induced by PTHrP(1-36). HG and PTHrP(1-36)-induced hypertrophy were associated with an increase in cyclin D1 and p27Kip1 protein expression, a decreased cyclin E expression, and the prevention of cyclin E/cdk2 complex activation. Both PTHrP neutralizing antiserum (α-PTHrP) and the PTH/PTHrP receptor antagonist (JB4250) were able to abolish HG induction of hypertrophy, the aforementioned changes in cell cycle proteins, and also TGF-β1 up-regulation. Moreover, the capability of both HG and PTHrP(1-36) to induce HMC hypertrophy was abolished by α-TGFβ1. These data show for the first time that PTHrP is upregulated in the kidney of patients with DN. Our findings also demonstrate that PTHrP acts as an important mediator of HG-induced HMC hypertrophy by modulating cell cycle regulatory proteins and TGF-β1.

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Role of the Renin-Angiotensin System on the Parathyroid Hormone–Related Protein Overexpression Induced by Nephrotoxic Acute Renal Failure in the Rat

Cited by 44 publications

References 31 publications

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

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

Modeled gravitational unloading induced downregulation of endothelin‐1 in human endothelial cells

Parathyroid hormone‐related protein is a hypertrophy factor for human mesangial cells: Implications for diabetic nephropathy

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