scholarly journals Role of Platelet-Derived Transforming Growth Factor-β1 and Reactive Oxygen Species in Radiation-Induced Organ Fibrosis

2017 ◽  
Vol 27 (13) ◽  
pp. 977-988 ◽  
Author(s):  
Jasimuddin Ahamed ◽  
Jeffrey Laurence
Keyword(s):  
Reactive Oxygen Species ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Reactive Oxygen ◽  
Transforming Growth Factor Β1 ◽  
Oxygen Species ◽  
Radiation Induced ◽  
Organ Fibrosis

scholarly journals GPCR transactivation signalling in vascular smooth muscle cells: role of NADPH oxidases and reactive oxygen species

2019 ◽  
Vol 1 (1) ◽  
pp. R1-R11 ◽  
Author(s):  
Raafat Mohamed ◽  
Reearna Janke ◽  
Wanru Guo ◽  
Yingnan Cao ◽  
Ying Zhou ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Growth Factor ◽  
Drug Targets ◽  
Protein Tyrosine Kinase ◽  
Transforming Growth Factor ◽  
Growth Factor Receptor ◽  
Reactive Oxygen ◽  
Transforming Growth Factor Β ◽  
Oxygen Species

The discovery and extension of G-protein-coupled receptor (GPCR) transactivation-dependent signalling has enormously broadened the GPCR signalling paradigm. GPCRs can transactivate protein tyrosine kinase receptors (PTKRs) and serine/threonine kinase receptors (S/TKRs), notably the epidermal growth factor receptor (EGFR) and transforming growth factor-β type 1 receptor (TGFBR1), respectively. Initial comprehensive mechanistic studies suggest that these two transactivation pathways are distinct. Currently, there is a focus on GPCR inhibitors as drug targets, and they have proven to be efficacious in vascular diseases. With the broadening of GPCR transactivation signalling, it is therefore important from a therapeutic perspective to find a common transactivation pathway of EGFR and TGFBR1 that can be targeted to inhibit complex pathologies activated by the combined action of these receptors. Reactive oxygen species (ROS) are highly reactive molecules and they act as second messengers, thus modulating cellular signal transduction pathways. ROS are involved in different mechanisms of GPCR transactivation of EGFR. However, the role of ROS in GPCR transactivation of TGFBR1 has not yet been studied. In this review, we will discuss the involvement of ROS in GPCR transactivation-dependent signalling.

scholarly journals Melatonin Prevents Transforming Growth Factor-β1-Stimulated Transdifferentiation of Renal Interstitial Fibroblasts to Myofibroblasts by Suppressing Reactive Oxygen Species-Dependent Mechanisms

Antioxidants ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 39 ◽  
Author(s):  
Jung-Yeon Kim ◽  
Jae-Hyung Park ◽  
Eon Ju Jeon ◽  
Jaechan Leem ◽  
Kwan-Kyu Park
Keyword(s):  
Reactive Oxygen Species ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Reactive Oxygen ◽  
Transforming Growth Factor Β1 ◽  
Membrane Receptors ◽  
Oxygen Species ◽  
Protective Effects ◽  
Independent Manner ◽  
Tgf Β1

Accumulating evidence suggests that the pineal hormone melatonin displays protective effects against renal fibrosis, but the mechanisms remain poorly understood. Here, we investigate the effect of the pineal hormone on transdifferentiation of renal fibroblasts to myofibroblasts invoked by transforming growth factor-β1 (TGF-β1). Increased proliferation and activation of renal interstitial fibroblasts after TGF-β1 treatment were attenuated by melatonin pretreatment. Mechanistically, melatonin suppressed Smad2/3 phosphorylation and nuclear co-localization of their phosphorylated forms and Smad4 after TGF-β1 stimulation. In addition, increased phosphorylations of Akt, extracellular signal-regulated kinase 1/2, and p38 after TGF-β1 treatment were also suppressed by the hormone. These effects of melatonin were not affected by pharmacological and genetic inhibition of its membrane receptors. Furthermore, melatonin significantly reversed an increase of intracellular reactive oxygen species (ROS) and malondialdehyde levels, and a decrease of the reduced glutathione/oxidized glutathione ratio after TGF-β1 treatment. Finally, TGF-β1-induced proliferation and activation were also suppressed by N-acetylcysteine. Altogether, these findings suggest that the pineal hormone melatonin prevents TGF-β1-induced transdifferentiation of renal interstitial fibroblasts to myofibroblasts via inhibition of Smad and non-Smad signaling cadcades by inhibiting ROS-mediated mechanisms in its receptor-independent manner.

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