Reactive oxygen species mediate TGF-β1-induced plasminogen activator inhibitor-1 upregulation in mesangial cells

2003 ◽  
Vol 309 (4) ◽  
pp. 961-966 ◽  
Author(s):  
Zongpei Jiang ◽  
Ji Yeon Seo ◽  
Hunjoo Ha ◽  
Eun Ah Lee ◽  
Yu Seun Kim ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Plasminogen Activator ◽  
Mesangial Cells ◽  
Reactive Oxygen ◽  
Plasminogen Activator Inhibitor ◽  
Oxygen Species ◽  
Plasminogen Activator Inhibitor 1 ◽  
Activator Inhibitor ◽  
Tgf Β1

Reactive oxygen species modulate HIF-1 mediated PAI-1 expression: involvement of the GTPase Rac1

2003 ◽  
Vol 89 (05) ◽  
pp. 926-935 ◽  
Author(s):  
Utta Berchner-Pfannschmidt ◽  
Christoph Wotzlaw ◽  
Robbert Cool ◽  
Joachim Fandrey ◽  
Helmut Acker ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Plasminogen Activator Inhibitor ◽  
Dominant Negative ◽  
Mrna Levels ◽  
Ros Production ◽  
Oxygen Species ◽  
Plasminogen Activator Inhibitor 1 ◽  
Pai 1

SummaryThe hypoxia-inducible transcription factor HIF-1 mediates upregulation of plasminogen activator inhibitor-1 (PAI-1) expression under hypoxia. Reactive oxygen species (ROS) have also been implicated in PAI-1 gene expression. However, the role of ROS in HIF-1-mediated regulation of PAI-1 is not clear. We therefore investigated the role of the GTPase Rac1 which modulates ROS production in the pathway leading to HIF-1 and PAI-1 induction.Overexpression of constitutively activated (RacG12V) or dominant-negative (RacT17N) Rac1 increased or decreased, respectively, ROS production. In RacG12V-expressing cells, PAI-1 mRNA levels as well as HIF-1α nuclear presence were reduced under normoxia and hypoxia whereas expression of RacT17N resulted in opposite effects. Treatment with the antioxidant pyrrolidinedithiocarbamate or coexpression of the redox factor-1 restored HIF-1 and PAI-1 promoter activity in RacG12V-cells. In contrast, NFκB activation was enhanced in RacG12V-cells, but abolished by RacT17N. Thus, these findings suggest a mechanism explaining modified fibrinolysis and tissue remodeling in an oxidized environment.

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.

Sign in / Sign up

Export Citation Format

Share Document