Reactive oxygen species and fibrosis: further evidence of a significant liaison

Richter, Kati; Kietzmann, Thomas

doi:10.1007/s00441-016-2445-3

Cited by 242 publications

(191 citation statements)

References 175 publications

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“…This was associated with ROS and profibrotic response2627. TGF-β1-mediated differentiation of fibroblasts is associated with increased mitochondrial content and cellular respiration28.…”

Section: Discussionmentioning

confidence: 99%

Myofibroblast differentiation and its functional properties are inhibited by nicotine and e-cigarette via mitochondrial OXPHOS complex III

Lei

Lerner

Sundar

et al. 2017

Sci Rep

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Nicotine is the major stimulant in tobacco products including e-cigarettes. Fibroblast to myofibroblast differentiation is a key process during wound healing and is dysregulated in lung diseases. The role of nicotine and e-cigarette derived nicotine on cellular functions including profibrotic response and other functional aspects is not known. We hypothesized that nicotine and e-cigarettes affect myofibroblast differentiation, gel contraction, and wound healing via mitochondria stress through nicotinic receptor-dependent mechanisms. To test the hypothesis, we exposed human lung fibroblasts with various doses of nicotine and e-cigarette condensate and determined myofibroblast differentiation, mitochondrial oxidative phosphorylation (OXPHOS), wound healing, and gel contraction at different time points. We found that both nicotine and e-cigarette inhibit myofibroblast differentiation as shown by smooth muscle actin and collagen type I, alpha 1 abundance. Nicotine and e-cigarette inhibited OXPHOS complex III accompanied by increased MitoROS, and this effect was augmented by complex III inhibitor antimycin A. These mitochondrial associated effects by nicotine resulted in inhibition of myofibroblast differentiation. These effects were associated with inhibition of wound healing and gel contraction suggesting that nicotine is responsible for dysregulated repair during injurious responses. Thus, our data suggest that nicotine causes dysregulated repair by inhibition of myofibroblast differentiation via OXPHOS pathway.

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“…This was associated with ROS and profibrotic response2627. TGF-β1-mediated differentiation of fibroblasts is associated with increased mitochondrial content and cellular respiration28.…”

Section: Discussionmentioning

confidence: 99%

Myofibroblast differentiation and its functional properties are inhibited by nicotine and e-cigarette via mitochondrial OXPHOS complex III

Lei

Lerner

Sundar

et al. 2017

Sci Rep

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“…Excessive ROS formation by mitochondria and/or other sources is well-known to promote interstitial and perivascular fibrosis 28. In addition, cardiac resident mast cell activation may contribute to fibrotic remodeling of the cardiac tissue 29, 30.…”

Section: Introductionmentioning

confidence: 99%

Monoamine oxidase-dependent endoplasmic reticulum-mitochondria dysfunction and mast cell degranulation lead to adverse cardiac remodeling in diabetes

Deshwal

Forkink

et al. 2018

Cell Death Differ

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Monoamine oxidase (MAO) inhibitors ameliorate contractile function in diabetic animals, but the mechanisms remain unknown. Equally elusive is the interplay between the cardiomyocyte alterations induced by hyperglycemia and the accompanying inflammation. Here we show that exposure of primary cardiomyocytes to high glucose and pro-inflammatory stimuli leads to MAO-dependent increase in reactive oxygen species that causes permeability transition pore opening and mitochondrial dysfunction. These events occur upstream of endoplasmic reticulum (ER) stress and are abolished by the MAO inhibitor pargyline, highlighting the role of these flavoenzymes in the ER/mitochondria cross-talk. In vivo, streptozotocin administration to mice induced oxidative changes and ER stress in the heart, events that were abolished by pargyline. Moreover, MAO inhibition prevented both mast cell degranulation and altered collagen deposition, thereby normalizing diastolic function. Taken together, these results elucidate the mechanisms underlying MAO-induced damage in diabetic cardiomyopathy and provide novel evidence for the role of MAOs in inflammation and inter-organelle communication. MAO inhibitors may be considered as a therapeutic option for diabetic complications as well as for other disorders in which mast cell degranulation is a dominant phenomenon.

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“…Over-activation of TGF-β1/Smad3 induces extracellular matrix (ECM) accumulation, fibrillar collagens deposition and elevated vascular cells viability, proliferation and migration, and ultimately results in vascular structural and functional alterations25. On the other hand, activation of dimer TGF-β1 is partially modulated by ROS26. The therapeutic effect of attenuating oxidative stress and preventing TGF-β1 during vascular remodeling in hypertension has been empirically proved272829.…”

mentioning

confidence: 99%

Acetyl-11-Keto-β-Boswellic Acid Attenuates Prooxidant and Profibrotic Mechanisms Involving Transforming Growth Factor-β1, and Improves Vascular Remodeling in Spontaneously Hypertensive Rats

Shang

Liu

et al. 2016

Sci Rep

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Vascular remodeling is an important complication of hypertension with oxidative stress-related profibrotic pathways involved. The transforming growth factor β1 (TGF-β1) has been shown to be a potential target of vasoprotection, and has multiple roles in vascular remodeling. Acetyl-11-Keto-β-Boswellic Acid (AKBA) is one of the active principles of Boswellic acids, and shows antioxidant activity in many diseases. The study is to determine effects of AKBA on systemic oxidative stress of hypertension and vascular remodeling. In the experiments, spontaneously hypertensive rats (SHR) were used. And in vitro, fibroblast was pretreated with AKBA before Ang II stimuli. In the results, treatment of AKBA markedly reduced oxidative stress, and decreased vascular remodeling by restoring vascular wall parameters and improving vascular reactivity. AKBA dramatically reduced TGF-β1 and Smad3 expression, as shown in immunofluorescence and immunohistochemistry. In cultured fibroblast, AKBA decreased intracellular ROS levels. Cell viability and proliferation, as well as migration were inhibited by AKBA. Additionally, treatment of AKBA significantly decreased TGF-β1 secretion in culture supernatant. Expression of TGF-β1, Smad3, P-Smad3 and Smad7 were also decreased by AKBA in fibroblast. In conclusion, AKBA is able to attenuate oxidative stress and profibrotic mechanisms, and improve vascular remodeling in hypertension through TGF-β1/Smad3 pathway.

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Reactive oxygen species and fibrosis: further evidence of a significant liaison

Cited by 242 publications

References 175 publications

Myofibroblast differentiation and its functional properties are inhibited by nicotine and e-cigarette via mitochondrial OXPHOS complex III

Myofibroblast differentiation and its functional properties are inhibited by nicotine and e-cigarette via mitochondrial OXPHOS complex III

Monoamine oxidase-dependent endoplasmic reticulum-mitochondria dysfunction and mast cell degranulation lead to adverse cardiac remodeling in diabetes

Acetyl-11-Keto-β-Boswellic Acid Attenuates Prooxidant and Profibrotic Mechanisms Involving Transforming Growth Factor-β1, and Improves Vascular Remodeling in Spontaneously Hypertensive Rats

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