Cellular and molecular mechanisms in the pathophysiology of systemic sclerosis

Hua-Huy, T.; Dinh-Xuan, Anh Tuan

doi:10.1016/j.patbio.2015.03.003

Cited by 24 publications

(13 citation statements)

References 101 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Myofibroblast activation in SSc has been demonstrated in pericytes and smooth muscle cells (SMCs) from vessel walls, resident fibroblasts, and bone marrow-derived fibroblasts ( 17 , 81 , 82 ). Although the ontogenesis of myofibroblasts in fibrotic conditions remains an area of active research ( 4 , 83 – 86 ), an increasing number of studies indicated EMT as a potential source of activated fibroblasts by which epithelial cells transform into myofibroblasts ( 5 – 8 , 14 , 15 ).…”

Section: Introductionmentioning

confidence: 99%

“…During the conversion of endothelium into mesenchyme elicited by TGF-β or Notch ligands, endothelial cells undergo morphological alterations and loss of characteristic cell-surface markers, acquiring mesenchymal, fibroblast-like properties such as spindle-shaped morphology, migratory capacity, invasiveness, and enhanced resistance to apoptosis ( 82 , 112 ). During EndMT, the structure of vessel-lining is disrupted due to resident endothelial cells disaggregating from the organized cells layer in the vessel walls and invading the surrounding tissue ( 112 – 114 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2018

View full text Add to dashboard Cite

Systemic sclerosis (SSc), an autoimmune disease that is associated with a number of genetic and environmental risk factors, is characterized by progressive fibrosis and microvasculature damage in the skin, lungs, heart, digestive system, kidneys, muscles, joints, and nervous system. These abnormalities are associated with altered secretion of growth factor and profibrotic cytokines, such as transforming growth factor-beta (TGF-β), interleukin-4 (IL-4), platelet-derived growth factor (PDGF), and connective-tissue growth factor (CTGF). Among the cellular responses to this proinflammatory environment, the endothelial cells phenotypic conversion into activated myofibroblasts, a process known as endothelial to mesenchymal transition (EndMT), has been postulated. Reactive oxygen species (ROS) might play a key role in SSs-associated fibrosis and vascular damage by mediating and/or activating TGF-β-induced EndMT, a phenomenon that has been observed in other disease models. In this review, we identified and critically appraised published studies investigating associations ROS and EndMT and the presence of EndMT in SSc, highlighting a potential link between oxidative stress and EndMT in this condition.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Inflammatory infiltrates are observed in a variety of affected organs and are accompanied by elevated circulating levels of inflammatory cytokines and chemokines. 2 Although activation of the immune system and inflammation modulate the systemic acute phase reaction and the hepatic acute phase protein response, the role of acute phase reactants for identifying inflammation in SSc have received little attention to date. 3 , 4 Some authors have indicated that the acute phase response is impaired in patients with SSc.…”

Section: Introductionmentioning

confidence: 99%

High acute phase protein levels correlate with pulmonary and skin involvement in patients with diffuse systemic sclerosis

et al. 2018

View full text Add to dashboard Cite

ObjectiveThis study was performed to evaluate the serum amyloid A (SAA) and C-reactive protein (CRP) levels in patients with diffuse systemic sclerosis (dSSc) in relation to a control group, disease duration, and skin and pulmonary involvement.MethodsThis case-control study included 18 patients with early dSSc, 15 patients with late dSSc, and 15 healthy controls. The SAA and CRP levels, modified Rodnan skin score (mRSS), and diffusing capacity of the lungs for carbon monoxide (DLCO) were determined in all patients.ResultsThe SAA and CRP levels were significantly higher in patients with early and late dSSc than in healthy controls. The frequency of detection of elevated SAA and CRP levels was approximately 66% and 85%, respectively. A significant correlation was found between the SAA and CRP levels in patients with dSSc. The SAA and CRP levels were inversely correlated with DLCO. The CRP level was positively correlated with the mRSS.ConclusionsHigh SAA and CRP levels could serve as biomarkers for pulmonary involvement. The serum CRP level accurately reflects the extension of skin thickening in patients with dSSc.

show abstract

“…The early phase of SSc is characterized by perivascular mononuclear cell infiltration (Mostmans et al, 2017) and the activation of the innate and adaptive immune system, which results in B-cell and T-cell activation (Amico et al, 2015). These cells secrete pro-inflammatory cytokines (including IL-1, IL-6, and IL-8) and chemokines that further stimulate ROS production (Murrell, 1993; Hua-Huy and Dinh-Xuan, 2015). However, ROS have been reported to promote activation of a variety of inflammation-associated transcription factors (e.g., nuclear factor-kappa B [NF-κB], activator protein-1 [AP-1], p53, signal transducer and activator of transcriptions 3 [STAT3], HIF-1α, and NF-E2 related factor-2 [Nrf2]).…”

Section: The Role Of Oxidative Stress In Ssc Vasculopathymentioning

confidence: 99%

The Role of Oxidative Stress in the Development of Systemic Sclerosis Related Vasculopathy

et al. 2018

View full text Add to dashboard Cite

Systemic sclerosis (SSc) is a rare connective tissue disease characterized by autoimmunity, vasculopathy, and progressive fibrosis typically affecting multiple organs including the skin. SSc often is a lethal disorder, because effective disease-modifying treatment still remains unavailable. Vasculopathy with endothelial dysfunction, perivascular infiltration of mononuclear cells, vascular wall remodeling and rarefaction of capillaries is the hallmark of the disease. Most patients present with vasospastic attacks of the digital arteries referred to as ‘Raynaud’s phenomenon,’ which is often an indication of an underlying widespread vasculopathy. Although autoimmune responses and inflammation are both found to play an important role in the pathogenesis of this vasculopathy, no definite initiating factors have been identified. Recently, several studies have underlined the potential role of oxidative stress in the pathogenesis of SSc vasculopathy thereby proposing a new aspect in the pathogenesis of this disease. For instance, circulating levels of reactive oxygen species (ROS) related markers have been found to correlate with SSc vasculopathy, the formation of fibrosis and the production of autoantibodies. Excess ROS formation is well-known to lead to endothelial cell (EC) injury and vascular complications. Collectively, these findings suggest a potential role of ROS in the initiation and progression of SSc vasculopathy. In this review, we present the background of oxidative stress related processes (e.g., EC injury, autoimmunity, inflammation, and vascular wall remodeling) that may contribute to SSc vasculopathy. Finally, we describe the use of oxidative stress related read-outs as clinical biomarkers of disease activity and evaluate potential anti-oxidative strategies in SSc.

show abstract

Cellular and molecular mechanisms in the pathophysiology of systemic sclerosis

Cited by 24 publications

References 101 publications

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

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

High acute phase protein levels correlate with pulmonary and skin involvement in patients with diffuse systemic sclerosis

The Role of Oxidative Stress in the Development of Systemic Sclerosis Related Vasculopathy

Contact Info

Product

Resources

About