Effects of parathyroid hormone-related protein on human mesangial cells in culture

1999 ◽  
Vol 277 (6) ◽  
pp. E990-E995 ◽  
Author(s):  
Ricardo J. Bosch ◽  
Pilar Rojo-Linares ◽  
Guadalupe Torrecillas-Casamayor ◽  
M. Carmen Iglesias-Cruz ◽  
Diego Rodríguez-Puyol ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Mesangial Cells ◽  
Biological Effects ◽  
Human Kidney ◽  
Kidney Cortex ◽  
Dependent Manner ◽  
Related Protein ◽  
Human Mesangial Cells ◽  
Parathyroid Hormone Related Protein ◽  
Pthrp Receptor

Parathyroid hormone (PTH) and PTH-related protein (PTHrP) produce similar biological effects through the PTH/PTHrP receptor. Because PTHrP exhibits vasodilatory properties, we evaluated the hypothesis that this hormone interacts with human mesangial cells (HMC). The PTHrP prevented both the expected reduction in the planar cell surface area and the increase in myosin light-chain phosphorylation induced by platelet-activating factor (PAF) on HMC, in a dose-dependent manner. This effect was completely blocked by pertussis toxin and dideoxyadenosine, suggesting that a G protein-coupled receptor and cAMP are important in the PTHrP transduction mechanism. Moreover, PTHrP increased cAMP synthesis and thymidine incorporation in HMC. However, whereas RT-PCR and Southern and Northern blot analyses demonstrated the expression of human PTH/PTHrP receptor in human kidney cortex, no expression could be demonstrated in HMC. These results show that PTH and PTHrP directly interact with mesangial cells. These effects might be mediated by a receptor different from the PTH/PTHrP receptor.

scholarly journals Dual roles of parathyroid hormone related protein in TGF-β1 signaling and fibronectin up-regulation in mesangial cells

2017 ◽  
Vol 37 (5) ◽  
Author(s):  
Su-Zhen Wu ◽  
Si-Jun Yang ◽  
Hong-Min Chen ◽  
Fang-Fang Peng ◽  
Hong Yu ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Mesangial Cells ◽  
Inhibitory Effect ◽  
Related Protein ◽  
Dual Roles ◽  
Protein Levels ◽  
Parathyroid Hormone Related Protein ◽  
Pthrp Receptor ◽  
First Time ◽  
Tgf Β1

Little is known about the cross-talk between parathyroid hormone (PTH) related protein (PTHrP) and TGF-β1 in mesangial cells (MCs). Our results showed that PTHrP treatment (≤3 h) induced internalization of PTH1R (PTH/PTHrP receptor)–TβRII (TGF-β type 2 receptor) complex and suppressed TGF-β1-mediated Smad2/3 activation and fibronectin (FN) up-regulation. However, prolonged PTHrP treatment (12–48 h) failed to induce PTH1R–TβRII association and internalization. Total protein levels of PTH1R and TβRII were unaffected by PTHrP treatment. These results suggest that internalization of PTH1R and TβRII after short PTHrP treatment might not lead to their proteolytic destruction, allowing the receptors to be recycled back to the plasma membrane during prolonged PTHrP exposure. Receptor re-expression at the cell surface allows PTHrP to switch from its initial inhibitory effect to promote induction of FN. Our study thus demonstrates the dual roles of PTHrP on TGF-β1 signaling and FN up-regulation for the first time in glomerular MCs. These data also provided new insights to guide development of therapy for diabetic kidney disease (DKD).

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

2012 ◽  
Vol 227 (5) ◽  
pp. 1980-1987 ◽  
Author(s):  
Arantxa Ortega ◽  
Montserrat Romero ◽  
Adriana Izquierdo ◽  
Nuria Troyano ◽  
Yolanda Arce ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Parathyroid Hormone ◽  
Mesangial Cells ◽  
Related Protein ◽  
Human Mesangial Cells ◽  
Parathyroid Hormone Related Protein

scholarly journals Parathyroid hormone-related protein induces fibronectin up-regulation in rat mesangial cells through reactive oxygen species/Src/EGFR signaling

2019 ◽  
Vol 39 (4) ◽  
Author(s):  
Hong-Min Chen ◽  
Jia-Jia Dai ◽  
Rui Zhu ◽  
Fang-Fang Peng ◽  
Su-Zhen Wu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Parathyroid Hormone ◽  
Mesangial Cells ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Related Protein ◽  
Egfr Signaling ◽  
Mesenchymal Transition ◽  
Parathyroid Hormone Related Protein ◽  
Tgf Β1

Abstract Parathyroid hormone-related protein (PTHrP) is known to be up-regulated in both glomeruli and tubules in patients with diabetic kidney disease (DKD), but its role remains unclear. Previous studies show that PTHrP-induced hypertrophic response in mesangial cells (MCs) and epithelial-mesenchymal transition (EMT) in tubuloepithelial cells can be mediated by TGF-β1. In the present study, although long-term PHTrP (1–34) treatment increased the mRNA and protein level of TGF-β1 in primary rat MCs, fibronectin up-regulation occurred earlier, suggesting that fibronectin induction is independent of TGF-β1/Smad signaling. We thus evaluated the involvement of epidermal growth factor receptor (EGFR) signaling and found that nicotinamide adenine dinucleotide phosphate oxidase-derived reactive oxygen species mediates PTHrP (1–34)-induced Src kinase activation. Src phosphorylates EGFR at tyrosine 845 and then transactive EGFR. Subsequent PI3K activation mediates Akt and ERK1/2 activation. Akt and ERK1/2 discretely lead to excessive protein synthesis of fibronectin. Our study thus demonstrates the new role of PTHrP in fibronectin up-regulation for the first time in glomerular MCs. These data also provided new insights to guide development of therapy for glomerular sclerosis.

scholarly journals Nitric oxide as a second messenger in parathyroid hormone-related protein signaling

2001 ◽  
Vol 170 (2) ◽  
pp. 433-440 ◽  
Author(s):  
L Kalinowski ◽  
LW Dobrucki ◽  
T Malinski
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Parathyroid Hormone ◽  
Smooth Muscles ◽  
Calcium Ionophore ◽  
No Production ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein ◽  
No Release ◽  
Pthrp Receptor

Parathyroid hormone (PTH)-related protein (PTHrP) is produced in smooth muscles and endothelial cells and is believed to participate in the local regulation of vascular tone. No direct evidence for the activation of endothelium-derived nitric oxide (NO) signaling pathway by PTHrP has been found despite attempts to identify it. Based on direct in situ measurements, it is reported here for the first time that the human PTH/PTHrP receptor analogs, hPTH(1--34) and hPTHrP(1--34), stimulate NO release from a single endothelial cell. A highly sensitive porphyrinic microsensor with a response time of 0.1 ms and a detection limit of 1 nmol/l was used for the measurement of NO. Both hPTH(1--34) and hPTHrP(1--34) stimulated NO release at nanomolar concentrations. The peak concentration of 0.1 micromol/l hPTH(1--34)- and 0.1 micromol/l hPTHrP(1--34)-stimulated NO release was 175+/-9 and 248+/-13 nmol/l respectively. This represents about 30%--40% of maximum NO concentration recorded in the presence of (0.1 micromol/l) calcium ionophore. Two competitive PTH/PTHrP receptor antagonists, 10 micromol/l [Leu(11),d -Trp(12)]-hPTHrP(7--34)amide and 10 micromol/l [Nle(8,18),Tyr(34)]-bPTH(3--34)amide, were equipotent in antagonizing hPTH(1--34)-stimulated NO release; [Leu(11),d -Trp(12)]-hPTHrP(7--34)amide was more potent than [Nle(8,18),Tyr(34)]-bPTH(3--34)amide in inhibiting hPTHrP(1--34)-stimulated NO release. The PKC inhibitor, H-7 (50 micromol/l), did not change hPTH(1--34)- and hPTHrP(1--34)-stimulated NO release, whereas the combined effect of 10 micromol/l of the cAMP antagonist, Rp-cAMPS, and 50 micromol/l of the calmodulin inhibitor, W-7, was additive. The present studies show that both hPTH(1--34) and hPTHrP(1--34) activate NO production in endothelial cells. The activation of NO release is through PTH/PTHrP receptors and is mediated via the calcium/calmodulin pathway.

Parathyroid hormone-related protein maintains mammary epithelial fate and triggers nipple skin differentiation during embryonic breast development

Development ◽  
2001 ◽  
Vol 128 (4) ◽  
pp. 513-525 ◽  
Author(s):  
J. Foley ◽  
P. Dann ◽  
J. Hong ◽  
J. Cosgrove ◽  
B. Dreyer ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Epithelial Cells ◽  
Cell Fate ◽  
Mesenchymal Cells ◽  
Mammary Development ◽  
Mammary Epithelial ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein ◽  
Mammary Mesenchyme ◽  
Pthrp Receptor

Prior reports have demonstrated that both parathyroid hormone-related protein (PTHrP) and the type I PTH/PTHrP receptor are necessary for the proper development of the embryonic mammary gland in mice. Using a combination of loss-of-function and gain-of-function models, we now report that PTHrP regulates a series of cell fate decisions that are central to the survival and morphogenesis of the mammary epithelium and the formation of the nipple. PTHrP is made in the epithelial cells of the mammary bud and, during embryonic mammary development, it interacts with the surrounding mesenchymal cells to induce the formation of the dense mammary mesenchyme. In response, these mammary-specific mesenchymal cells support the maintenance of mammary epithelial cell fate, trigger epithelial morphogenesis and induce the overlying epidermis to form the nipple. In the absence of PTHrP signaling, the mammary epithelial cells revert to an epidermal fate, no mammary ducts are formed and the nipple does not form. In the presence of diffuse epidermal PTHrP signaling, the ventral dermis is transformed into mammary mesenchyme and the entire ventral epidermis becomes nipple skin. These alterations in cell fate require that PTHrP be expressed during development and they require the presence of the PTH/PTHrP receptor. Finally, PTHrP signaling regulates the epidermal and mesenchymal expression of LEF1 and (β)-catenin, suggesting that these changes in cell fate involve an interaction between the PTHrP and Wnt signaling pathways.

scholarly journals Renal expression of parathyroid hormone-related protein (PTHrP) and PTH/PTHrP receptor in a rat model of tubulointerstitial damage

1999 ◽  
Vol 55 (1) ◽  
pp. 82-90 ◽  
Author(s):  
Raquel Largo ◽  
Dulcenombre Gómez-Garre ◽  
Soledad Santos ◽  
Carlos Peñaranda ◽  
Julia Blanco ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Rat Model ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein ◽  
Tubulointerstitial Damage ◽  
Pthrp Receptor ◽  
Renal Expression
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