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 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).

scholarly journals Role of NADPH Oxidase-Mediated Reactive Oxygen Species in Podocyte Injury

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Shan Chen ◽  
Xian-Fang Meng ◽  
Chun Zhang
Keyword(s):  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Epithelial To Mesenchymal Transition ◽  
Kidney Diseases ◽  
Treatment Strategies ◽  
Reactive Oxygen ◽  
Glomerular Sclerosis ◽  
Oxygen Species ◽  
Podocyte Injury ◽  
Mesenchymal Transition

Proteinuria is an independent risk factor for end-stage renal disease (ESRD) (Shankland, 2006). Recent studies highlighted the mechanisms of podocyte injury and implications for potential treatment strategies in proteinuric kidney diseases (Zhang et al., 2012). Reactive oxygen species (ROS) are cellular signals which are closely associated with the development and progression of glomerular sclerosis. NADPH oxidase is a district enzymatic source of cellular ROS production and prominently expressed in podocytes (Zhang et al., 2010). In the last decade, it has become evident that NADPH oxidase-derived ROS overproduction is a key trigger of podocyte injury, such as renin-angiotensin-aldosterone system activation (Whaley-Connell et al., 2006), epithelial-to-mesenchymal transition (Zhang et al., 2011), and inflammatory priming (Abais et al., 2013). This review focuses on the mechanism of NADPH oxidase-mediated ROS in podocyte injury under different pathophysiological conditions. In addition, we also reviewed the therapeutic perspectives of NADPH oxidase in kidney diseases related to podocyte injury.

Cyclic stretch increases VEGF expression in pulmonary arterial smooth muscle cells via TGF-β1 and reactive oxygen species: a requirement for NAD(P)H oxidase

2005 ◽  
Vol 289 (2) ◽  
pp. L288-L289 ◽  
Author(s):  
Eugenia Mata-Greenwood ◽  
Albert Grobe ◽  
Sanjiv Kumar ◽  
Yelina Noskina ◽  
Stephen M. Black
Keyword(s):  
Reactive Oxygen Species ◽  
Blood Flow ◽  
Smooth Muscle ◽  
Reactive Oxygen ◽  
Cyclic Stretch ◽  
Oxygen Species ◽  
Vegf Expression ◽  
Pulmonary Vessels ◽  
Pulmonary Arterial ◽  
Tgf Β1

Our previous studies have indicated that transforming growth factor (TGF)-β1 and VEGF expression are increased in the smooth muscle cell (SMC) layer of the pulmonary vessels of lambs with pulmonary hypertension secondary to increased pulmonary blood flow. Furthermore, we found that TGF-β1 expression increased before VEGF. Because of the increased blood flow in the shunt lambs, the SMC in the pulmonary vessels are exposed to increased levels of the mechanical force, cyclic stretch. Thus, in this study, using primary cultures of pulmonary arterial SMC isolated from pulmonary arteries of 4-wk-old lambs, we investigated the role of cyclic stretch in the apparent coordinated regulation of TGF-β1 and VEGF. Our results demonstrated that cyclic stretch induced a significant increase in VEGF expression both at the mRNA and protein levels ( P < 0.05). The increased VEGF mRNA was preceded by both an increased expression and secretion of TGF-β1 and an increase in reactive oxygen species (ROS) generation. In addition, a neutralizing antibody against TGF-β1 abolished the cyclic stretch-dependent increases in both superoxide generation and VEGF expression. Our data also demonstrated that cyclic stretch activated an NAD(P)H oxidase that was TGF-β1 dependent and that NAD(P)H oxidase inhibitors abolished the cyclic stretch-dependent increase in VEGF expression. Therefore, our results indicate that cyclic stretch upregulates VEGF expression via the TGF-β1-dependent activation of NAD(P)H oxidase and increased generation of ROS.

Modulation of Intracellular Reactive Oxygen Species Level in Chondrocytes by IGF-1, FGF, and TGF-β1

2007 ◽  
Vol 48 (3) ◽  
pp. 149-158 ◽  
Author(s):  
Navid Jallali ◽  
Hyder Ridha ◽  
Christopher Thrasivoulou ◽  
Peter Butler ◽  
Timothy Cowen
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Intracellular Reactive Oxygen Species ◽  
Species Level ◽  
Reactive Oxygen Species Level ◽  
Oxygen Species ◽  
Tgf Β1
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