Free radical generation induces epithelial-to-mesenchymal transition in lung epithelium via a TGF-β1-dependent mechanism

Gorowiec, Marta R.; Borthwick, Lee A.; Parker, Sean; Kirby, John A.; Saretzki, Gabriele; Fisher, Andrew J.

doi:10.1016/j.freeradbiomed.2011.12.020

Cited by 99 publications

(54 citation statements)

References 57 publications

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“…It has been shown that ROS, such as superoxide radicals, can increase TGF-b1 and collagen release from lung fibroblasts [24]. More recently, Gorowiec et al present in vitro evidence for a role of oxidative stress as an initiator of TGFb1 expression and TGF-b1-dependent EMT induction in lung epithelial cells [25]. Collectively, these data let us suggest that pulmonary oxidative stress, the earliest detectable change after LPS administration, may act as a trigger for production of the profibrotic cytokine TGF-b1.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol ameliorates lipopolysaccharide-induced epithelial mesenchymal transition and pulmonary fibrosis through suppression of oxidative stress and transforming growth factor-β1 signaling

et al. 2015

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Section: Discussionmentioning

confidence: 99%

Resveratrol ameliorates lipopolysaccharide-induced epithelial mesenchymal transition and pulmonary fibrosis through suppression of oxidative stress and transforming growth factor-β1 signaling

et al. 2015

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“…In addition, collagen and cadherin, two profibrotic proteins induced by TGF-b1, have been shown to promote EMT (70,71). Furthermore, p38 MAPK activation, oxidative stress, endothelin-1, Wnt signaling, and cytokine signaling modulate TGF-b1-induced EMT (68,(72)(73)(74)(75)(76).…”

Section: Airway Remodeling and Proliferationmentioning

confidence: 99%

Transforming Growth Factor β1 Function in Airway Remodeling and Hyperresponsiveness. The Missing Link?

Ojiaku

Yoo

Panettieri

2017

Am J Respir Cell Mol Biol

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The pathogenesis of asthma includes a complex interplay among airway inflammation, hyperresponsiveness, and remodeling. Current evidence suggests that airway structural cells, including bronchial smooth muscle cells, myofibroblasts, fibroblasts, and epithelial cells, mediate all three aspects of asthma pathogenesis. Although studies show a connection between airway remodeling and changes in bronchomotor tone, the relationship between the two remains unclear. Transforming growth factor b1 (TGF-b1), a growth factor elevated in the airway of patients with asthma, plays a role in airway remodeling and in the shortening of various airway structural cells. However, the role of TGF-b1 in mediating airway hyperresponsiveness remains unclear. In this review, we summarize the literature addressing the role of TGF-b1 in airway remodeling and shortening. Through our review, we aim to further elucidate the role of TGF-b1 in asthma pathogenesis and the link between airway remodeling and airway hyperresponsiveness in asthma and to define TGF-b1 as a potential therapeutic target for reducing asthma morbidity and mortality.

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“…ROS also activate latent TGFβ1, which in turn fosters the production of more ROS91011. This intrinsic TGFβ1 cycle also promotes the epithelial mesenchymal transition (EMT), a process in which pulmonary epithelial cells transform to fibroblasts and myofibroblasts101213. The importance of ROS in PF is also highlighted by the fact that N-acetylcysteine, a glutathione precursor that inhibits that myofibroblast formation14, attenuated PF in an animal model15 and in combination with other drugs - the decline of lung function in a randomized trial of patients with idiopathic PF16.…”

mentioning

confidence: 99%

Time-dependent and somatically acquired mitochondrial DNA mutagenesis and respiratory chain dysfunction in a scleroderma model of lung fibrosis

Gazdhar

Lebrecht

Roth

et al. 2014

Sci Rep

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Reactive oxygen species (ROS) have been implemented in the etiology of pulmonary fibrosis (PF) in systemic sclerosis. In the bleomycin model, we evaluated the role of acquired mutations in mitochondrial DNA (mtDNA) and respiratory chain defects as a trigger of ROS formation and fibrogenesis. Adult male Wistar rats received a single intratracheal instillation of bleomycin and their lungs were examined at different time points. Ashcroft scores, collagen and TGFβ1 levels documented a delayed onset of PF by day 14. In contrast, increased malon dialdehyde as a marker of ROS formation was detectable as early as 24 hours after bleomycin instillation and continued to increase. At day 7, lung tissue acquired significant amounts of mtDNA deletions, translating into a significant dysfunction of mtDNA-encoded, but not nucleus-encoded respiratory chain subunits. mtDNA deletions and markers of mtDNA-encoded respiratory chain dysfunction significantly correlated with pulmonary TGFβ1 concentrations and predicted PF in a multivariate model.

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Free radical generation induces epithelial-to-mesenchymal transition in lung epithelium via a TGF-β1-dependent mechanism

Cited by 99 publications

References 57 publications

Resveratrol ameliorates lipopolysaccharide-induced epithelial mesenchymal transition and pulmonary fibrosis through suppression of oxidative stress and transforming growth factor-β1 signaling

Resveratrol ameliorates lipopolysaccharide-induced epithelial mesenchymal transition and pulmonary fibrosis through suppression of oxidative stress and transforming growth factor-β1 signaling

Transforming Growth Factor β1 Function in Airway Remodeling and Hyperresponsiveness. The Missing Link?

Time-dependent and somatically acquired mitochondrial DNA mutagenesis and respiratory chain dysfunction in a scleroderma model of lung fibrosis

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