scholarly journals Adenosine 5′-triphosphate stimulates the increase of TGF-β1 in rat mesangial cells under high-glucose conditions via reactive oxygen species and ERK1/2

2009 ◽  
Vol 30 (12) ◽  
pp. 1601-1606 ◽  
Author(s):  
Lin-ping Qu ◽  
Hong Xue ◽  
Ping Yuan ◽  
Li Zhou ◽  
Tai Yao ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
High Glucose ◽  
Mesangial Cells ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Tgf Β1

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.

Angiotensin II Mediates High Glucose-Induced TGF-β1 and Fibronectin Upregulation in HPMC through Reactive Oxygen Species

2005 ◽  
Vol 25 (1) ◽  
pp. 38-47 ◽  
Author(s):  
Hyunjin Noh ◽  
Hunjoo Ha ◽  
Mi Ra Yu ◽  
Young Ok Kim ◽  
Ji Hye Kim ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Protein Expression ◽  
High Glucose ◽  
Reactive Oxygen ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Ang Ii ◽  
Fibronectin Expression ◽  
Tgf Β1

Objective To demonstrate the presence of an independent renin–angiotensin system (RAS) in the peritoneum and to determine the role of locally produced angiotensin (Ang) II in high glucose-induced upregulation of transforming growth factor (TGF)-β1 and fibronectin by human peritoneal mesothelial cells (HPMC). Methods In cultured HPMC, the expression of mRNAs for angiotensinogen, angiotensin-converting enzyme (ACE), Ang II type 1 receptor (AT1), and TGF-β1 was evaluated by real-time polymerase chain reaction; ACE, AT1, and fibronectin proteins by Western blot analysis; and Ang I, Ang II, and TGF-β1 proteins by ELISA. Dichlorofluorescein (DCF)-sensitive cellular reactive oxygen species (ROS) were measured by fluorometry. Results HPMC constitutively expressed all the components of RAS, and 50 mmol/L D-glucose (high glucose) significantly increased angiotensinogen, ACE, and AT1 mRNAs and ACE, AT1, and Ang II proteins. Ang II increased TGF-β1 and fibronectin protein expression and DCF-sensitive cellular ROS. Losartan prevented Ang II-induced increase in cellular ROS. Both losartan and captopril inhibited high glucose-induced upregulation of TGF-β1 and fibronectin expression in HPMC in a dose-dependent manner. Antioxidant catalase and NADPH oxidase inhibitor diphenyleneiodinium effectively inhibited Ang II-induced TGF-β1 and fibronectin protein expression. Conclusions The present data demonstrate that HPMC constitutively express RAS, that Ang II produced by HPMC mediates high glucose-induced upregulation of TGF-β1 and fibronectin expression, and that Ang II-induced TGF-β1 and fibronectin expression in HPMC is mediated by NADPH oxidase-dependent ROS. These data suggest that locally produced Ang II and ROS in the peritoneum may be potential therapeutic targets in peritoneal fibrosis during long-term peritoneal dialysis.

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