scholarly journals A Transgenic Mouse Model for Studying the Role of the Parathyroid Hormone-Related Protein System in Renal Injury

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Ricardo J. Bosch ◽  
Arantxa Ortega ◽  
Adriana Izquierdo ◽  
Ignacio Arribas ◽  
Jordi Bover ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Transgenic Mouse ◽  
Renal Injury ◽  
Renal Diseases ◽  
Obstructive Nephropathy ◽  
Protective Effects ◽  
Ang Ii ◽  
Related Protein ◽  
Renal Hypertrophy ◽  
Parathyroid Hormone Related Protein

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.

scholarly journals Novel Role of Parathyroid Hormone-Related Protein in the Pathophysiology of the Diabetic Kidney: Evidence from Experimental and Human Diabetic Nephropathy

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Montserrat Romero ◽  
Arantxa Ortega ◽  
Nuria Olea ◽  
María Isabel Arenas ◽  
Adriana Izquierdo ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Parathyroid Hormone ◽  
Renal Injury ◽  
Renal Diseases ◽  
Protective Effects ◽  
Ang Ii ◽  
Related Protein ◽  
Renal Hypertrophy ◽  
Glomerular Diseases ◽  
Parathyroid Hormone Related Protein

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-β1. 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.

scholarly journals Urinary excretion of parathyroid hormone-related protein correlates with renal function in control rats and rats with cisplatin nephrotoxicity

2019 ◽  
Vol 317 (4) ◽  
pp. F874-F880
Author(s):  
Arantxa Ortega ◽  
Nuria Olea-Herrero ◽  
M. Isabel Arenas ◽  
Esperanza Vélez-Vélez ◽  
Rafael Moreno-Gómez-Toledano ◽  
...  
Keyword(s):  
Renal Function ◽  
Parathyroid Hormone ◽  
Renal Injury ◽  
Protein Band ◽  
Related Protein ◽  
Dot Blot ◽  
Rat Urine ◽  
Cisplatin Nephrotoxicity ◽  
Parathyroid Hormone Related Protein ◽  
Injury And Repair

Parathyroid hormone-related protein (PTHrP) and its receptor are abundantly expressed throughout the renal parenchyma, where PTHrP exerts a modulatory action on renal function. PTHrP upregulation is a common event associated with the mechanism of renal injury and repair. However, no study has yet explored the putative excretion of PTHrP in urine, including its potential relationship with renal function. In the present study, we tested this hypothesis by studying the well-known rat model of acute renal injury induced by the chemotherapeutic agent cisplatin. Using Western blot analysis, we could detect a single protein band, corresponding to intact PTHrP, in the urine of both control and cisplatin-injected rats, whose levels were significantly higher in the latter group. PTHrP was detected in rat urine by dot blot, and its quantification with two specific ELISA kits showed that, compared with control rats, those treated with cisplatin displayed a significant increase in urinary PTHrP (expressed as the PTHrP-to-creatinine ratio or 24-h excretion). In addition, a positive correlation between urinary PTHrP excretion and serum creatinine was found in these animals. In conclusion, our data demonstrate that PTHrP is excreted in rat urine and that this excretion is higher with the decrease of renal function. This suggests that urinary PTHrP levels might be a renal function marker.

Parathyroid Hormone–Related Protein Inhibits Endothelin-1 Production

Hypertension ◽  
1996 ◽  
Vol 27 (3) ◽  
pp. 360-363 ◽  
Author(s):  
Bingbing Jiang ◽  
Shigeto Morimoto ◽  
Keisuke Fukuo ◽  
Atsushi Hirotani ◽  
Michio Tamatani ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Related Protein ◽  
Endothelin 1 ◽  
Parathyroid Hormone Related Protein

Parathyroid Hormone–Related Protein Upregulates Interleukin-1β–Induced Nitric Oxide Synthesis

Hypertension ◽  
1997 ◽  
Vol 30 (4) ◽  
pp. 922-927 ◽  
Author(s):  
Bingbing Jiang ◽  
Shigeto Morimoto ◽  
Jin Yang ◽  
Keisuke Fukuo ◽  
Atsushi Hirotani ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Parathyroid Hormone ◽  
Interleukin 1Β ◽  
Nitric Oxide Synthesis ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein

scholarly journals Purification and Characterization of Recombinant Human Parathyroid Hormone-related Protein

1989 ◽  
Vol 264 (25) ◽  
pp. 14806-14811
Author(s):  
R G Hammonds ◽  
P McKay ◽  
G A Winslow ◽  
H Diefenbach-Jagger ◽  
V Grill ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Related Protein ◽  
Human Parathyroid Hormone ◽  
Purification And Characterization ◽  
Parathyroid Hormone Related Protein

scholarly journals Extracellular vesicles-released parathyroid hormone-related protein from Lewis lung carcinoma induces lipolysis and adipose tissue browning in cancer cachexia

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wenjun Hu ◽  
Hairong Xiong ◽  
Zeyuan Ru ◽  
Yan Zhao ◽  
Yali Zhou ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Parathyroid Hormone ◽  
Lung Carcinoma ◽  
Lewis Lung Carcinoma ◽  
Cancer Cachexia ◽  
Lewis Lung ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein ◽  
Tissue Browning

AbstractCancer cachexia is a metabolic disorder characterized by skeletal muscle wasting and white adipose tissue browning. Specific functions of several hormones, growth factors, and cytokines derived from tumors can trigger cachexia. Moreover, adipose tissue lipolysis might explain weight loss that occurs owing to cachexia. Extracellular vesicles (EVs) are involved in intercellular communication. However, whether EVs participate in lipolysis induced by cancer cachexia has not been thoroughly investigated. Using Lewis lung carcinoma (LLC) cell culture, we tested whether LLC cell-derived EVs can induce lipolysis in 3T3-L1 adipocytes. EVs derived from LLC cells were isolated and characterized biochemically and biophysically. Western blotting and glycerol assay were used to study lipolysis. LLC cell-derived EVs induced lipolysis in vivo and vitro. EVs fused directly with target 3T3-L1 adipocytes and transferred parathyroid hormone-related protein (PTHrP), activating the PKA signaling pathway in 3T3-L1 adipocytes. Blocking PTHrP activity in LLC-EVs using a neutralizing antibody and by knocking down PTHR expression prevented lipolysis in adipocytes. Inhibiting the PKA signaling pathway also prevents the lipolytic effects of EVs. In vivo, suppression of LLC-EVs release by knocking down Rab27A alleviated white adipose tissue browning and lipolysis. Our data showed that LLC cell-derived EVs induced adipocyte lipolysis via the extracellular PTHrP-mediated PKA pathway. Our data demonstrate that LLC-EVs induce lipolysis in vitro and vivo by delivering PTHrP, which interacts with PTHR. The lipolytic effect of LLC-EVs was abrogated by PTHR knockdown and treatment with a neutralizing anti-PTHrP antibody. Together, these data show that LLC-EV-induced lipolysis is mediated by extracellular PTHrP. These findings suggest a novel mechanism of lipid droplet loss and identify a potential therapeutic strategy for cancer cachexia.

scholarly journals Parathyroid Hormone-Related Protein Induces Cachectic Syndromes without Directly Modulating the Expression of Hypothalamic Feeding-Regulating Peptides

2007 ◽  
Vol 13 (1) ◽  
pp. 292-298 ◽  
Author(s):  
Hirofumi Hashimoto ◽  
Yumiko Azuma ◽  
Makoto Kawasaki ◽  
Hiroaki Fujihara ◽  
Etsuro Onuma ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein
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