A Potential Link Between Oxidative Stress and Endothelial-to-Mesenchymal Transition in Systemic Sclerosis

Thuan, Duong Thi Bich; Zayed, Hatem; Eid, Ali H.; Abou-Saleh, Haissam; Nasrallah, Gheyath K.; Mangoni, Arduino A.; Pintus, Gianfranco

doi:10.3389/fimmu.2018.01985

Cited by 86 publications

(66 citation statements)

References 181 publications

(240 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mitochondrial-generated increase of ROS has been found to induce lung fibrosis [154,155]. Although a potentially vicious cycle of TGF-β and ROS interaction exists, where ROS activate TGF-β and TGF-β activates ROS [156][157][158]), TGF-β1 appears to be the most important trigger of mitochondrial (mtROS) production associated with the profibrotic phenotype reprogramming of lung cells [159]. This proposition is further supported by the observation that the deletion of NOX4 abrogates TGF-β1-induced fibrosis in mice [160].…”

Section: Mitochondrial Dysfunctionmentioning

confidence: 99%

Emerging cellular and molecular determinants of idiopathic pulmonary fibrosis

Phan

Paliogiannis

Nasrallah

et al. 2020

Cell. Mol. Life Sci.

Self Cite

236

152

View full text Add to dashboard Cite

Idiopathic pulmonary fibrosis (IPF), the most common form of idiopathic interstitial pneumonia, is a progressive, irreversible, and typically lethal disease characterized by an abnormal fibrotic response involving vast areas of the lungs. Given the poor knowledge of the mechanisms underpinning IPF onset and progression, a better understanding of the cellular processes and molecular pathways involved is essential for the development of effective therapies, currently lacking. Besides a number of established IPF-associated risk factors, such as cigarette smoking, environmental factors, comorbidities, and viral infections, several other processes have been linked with this devastating disease. Apoptosis, senescence, epithelial-mesenchymal transition, endothelial-mesenchymal transition, and epithelial cell migration have been shown to play a key role in IPF-associated tissue remodeling. Moreover, molecules, such as chemokines, cytokines, growth factors, adenosine, glycosaminoglycans, non-coding RNAs, and cellular processes including oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, hypoxia, and alternative polyadenylation have been linked with IPF development. Importantly, strategies targeting these processes have been investigated to modulate abnormal cellular phenotypes and maintain tissue homeostasis in the lung. This review provides an update regarding the emerging cellular and molecular mechanisms involved in the onset and progression of IPF.

show abstract

Section: Mitochondrial Dysfunctionmentioning

confidence: 99%

Emerging cellular and molecular determinants of idiopathic pulmonary fibrosis

Phan

Paliogiannis

Nasrallah

et al. 2020

Cell. Mol. Life Sci.

Self Cite

236

152

View full text Add to dashboard Cite

show abstract

“…In particular, EndMT has been implicated in the progression of subclinical atherosclerosis as “transitioning” cells and is readily detected in human plaques (117). Oxidative stress is known to be involved in EndMT and subsequent vascular damage through TGF-β (203). Brain Arnt-like protein-1 (BMAL1) suppresses ROS production and a positive relationship exists between loss of BMAL1 expression and EndMT in atherosclerotic plaque vulnerability in human carotid plaques.…”

Section: Ros and Resident Vascular Stem Cellsmentioning

confidence: 99%

Reactive Oxygen Species (ROS), Intimal Thickening, and Subclinical Atherosclerotic Disease

Burtenshaw

Kitching

Redmond

et al. 2019

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Arteriosclerosis causes significant morbidity and mortality worldwide. Central to this process is the development of subclinical non-atherosclerotic intimal lesions before the appearance of pathologic intimal thickening and advanced atherosclerotic plaques. Intimal thickening is associated with several risk factors, including oxidative stress due to reactive oxygen species (ROS), inflammatory cytokines and lipid. The main ROS producing systems in-vivo are reduced nicotinamide dinucleotide phosphate (NADPH) oxidase (NOX). ROS effects are context specific. Exogenous ROS induces apoptosis and senescence, whereas intracellular ROS promotes stem cell differentiation, proliferation, and migration. Lineage tracing studies using murine models of subclinical atherosclerosis have revealed the contributory role of medial smooth muscle cells (SMCs), resident vascular stem cells, circulating bone-marrow progenitors and endothelial cells that undergo endothelial-mesenchymal-transition (EndMT). This review will address the putative physiological and patho-physiological roles of ROS in controlling vascular cell fate and ROS contribution to vascular regeneration and disease progression.

show abstract

“…Oxidative stress can induce single-strand DNA breaks (SSBs) that can be converted to cytotoxic double-strand DNA breaks (DSBs) when replication forks come across SSBs. SSc patients are indeed characterized by increased ROS production in the skin, visceral fibroblasts, and endothelial cells ( 7 , 8 ). In turn, ROS can activate endothelial cells, leading to vascular hyper-reactivity, endothelial cell apoptosis, and impaired angiogenesis ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

Association Between DNA Damage Response, Fibrosis and Type I Interferon Signature in Systemic Sclerosis

et al. 2020

View full text Add to dashboard Cite

Increased endogenous DNA damage and type I interferon pathway activation have been implicated in systemic sclerosis (SSc) pathogenesis. Because experimental evidence suggests an interplay between DNA damage response/repair (DDR/R) and immune response, we hypothesized that deregulated DDR/R is associated with a type I interferon signature and/or fibrosis extent in SSc. DNA damage levels, oxidative stress, induction of abasic sites and the efficiency of DNA double-strand break repair (DSB/R) and nucleotide excision repair (NER) were assessed in peripheral blood mononuclear cells (PBMCs) derived from 37 SSc patients and 55 healthy controls; expression of DDR/R-associated genes and type I interferon–induced genes was also quantified. Endogenous DNA damage was significantly higher in untreated diffuse or limited SSc (Olive tail moment; 14.7 ± 7.0 and 9.5 ± 4.1, respectively) as well as in patients under cytotoxic treatment (15.0 ± 5.4) but not in very early onset SSc (5.6 ± 1.2) compared with controls (4.9 ± 2.6). Moreover, patients with pulmonary fibrosis had significantly higher DNA damage levels than those without (12.6 ± 5.8 vs. 8.8 ± 4.8, respectively). SSc patients displayed increased oxidative stress and abasic sites, defective DSB/R but not NER capacity, downregulation of genes involved in DSB/R (MRE11A, PRKDC) and base excision repair (PARP1, XRCC1), and upregulation of apoptosis-related genes (BAX, BBC3). Individual levels of DNA damage in SSc PBMCs correlated significantly with the corresponding mRNA expression of type I interferon–induced genes (IFIT1, IFI44 and MX1, r =0.419-0.490) as well as with corresponding skin involvement extent by modified Rodnan skin score ( r =0.481). In conclusion, defective DDR/R may exert a fuel-on-fire effect on type I interferon pathway activation and contribute to tissue fibrosis in SSc.

show abstract

A Potential Link Between Oxidative Stress and Endothelial-to-Mesenchymal Transition in Systemic Sclerosis

Cited by 86 publications

References 181 publications

Emerging cellular and molecular determinants of idiopathic pulmonary fibrosis

Emerging cellular and molecular determinants of idiopathic pulmonary fibrosis

Reactive Oxygen Species (ROS), Intimal Thickening, and Subclinical Atherosclerotic Disease

Association Between DNA Damage Response, Fibrosis and Type I Interferon Signature in Systemic Sclerosis

Contact Info

Product

Resources

About