scholarly journals Myrtol improves post‑traumatic knee osteoarthritis by regulation of reactive oxygen species, transforming growth factor β1 and apoptosis in a mouse model

2017 ◽  
Author(s):  
Liqun Duan ◽  
Wenzhi Zhang ◽  
Feng Zhang ◽  
Haiping Cai
Keyword(s):  
Reactive Oxygen Species ◽  
Growth Factor ◽  
Mouse Model ◽  
Knee Osteoarthritis ◽  
Transforming Growth Factor ◽  
Reactive Oxygen ◽  
Transforming Growth Factor Β1 ◽  
Oxygen Species ◽  
Post Traumatic

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.

scholarly journals Mitochondrial Reactive Oxygen Species Mediate GPCR–induced TACE/ADAM17-dependent Transforming Growth Factor-α Shedding

2009 ◽  
Vol 20 (24) ◽  
pp. 5236-5249 ◽  
Author(s):  
Timothy J. Myers ◽  
Leann H. Brennaman ◽  
Mary Stevenson ◽  
Shigeki Higashiyama ◽  
William E. Russell ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Ros Scavenging ◽  
Transforming Growth Factor Α ◽  
Egfr Activation ◽  
Mitochondrial Ros ◽  
Factor Α

Epidermal growth factor receptor (EGFR) activation by GPCRs regulates many important biological processes. ADAM metalloprotease activity has been implicated as a key step in transactivation, yet the regulatory mechanisms are not fully understood. Here, we investigate the regulation of transforming growth factor-α (TGF-α) shedding by reactive oxygen species (ROS) through the ATP-dependent activation of the P2Y family of GPCRs. We report that ATP stimulates TGF-α proteolysis with concomitant EGFR activation and that this process requires TACE/ADAM17 activity in both murine fibroblasts and CHO cells. ATP-induced TGF-α shedding required calcium and was independent of Src family kinases and PKC and MAPK signaling. Moreover, ATP-induced TGF-α shedding was completely inhibited by scavengers of ROS, whereas calcium-stimulated shedding was partially inhibited by ROS scavenging. Hydrogen peroxide restored TGF-α shedding after calcium chelation. Importantly, we also found that ATP-induced shedding was independent of the cytoplasmic NADPH oxidase complex. Instead, mitochondrial ROS production increased in response to ATP and mitochondrial oxidative complex activity was required to activate TACE-dependent shedding. These results reveal an essential role for mitochondrial ROS in regulating GPCR-induced growth factor shedding.

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