High reactive oxygen species in fibrotic and nonfibrotic skin of patients with diffuse cutaneous systemic sclerosis

Bourji, Khalil I.; Meyer, Alain; Chatelus, Emmanuel; Pincemaïl, Joël; Pigatto, Erika; Defraigne, Jean; Singh, François; Charlier, Corinne; Gény, Bernard; Gottenberg, Jacques Éric; Punzi, Leonardo; Cozzi, Franco; Sibilia, Jean

doi:10.1016/j.freeradbiomed.2015.07.002

Cited by 43 publications

(41 citation statements)

References 31 publications

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“…In contrast to the human pathology, we found an increase in subdermal fat especially in the HOCl‐induced Scl model. This ROS‐induced fat accumulation could not be observed in human sclerotic skin, although ROS levels in fibrotic and non‐fibrotic skin of patients with SSc are significantly higher than in healthy controls . SR staining revealed a pronounced loss of collagen organization with more newly formed, thinner fibres, cross‐links and densely packed fibre bundles after HOCl compared to bleomycin injection.…”

Section: Discussionmentioning

confidence: 79%

Myeloid cell populations and fibrogenic parameters in bleomycin‐ and HOCl‐induced fibrosis

Raker

Ook

Haub

et al. 2016

Experimental Dermatology

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Mouse models resembling systemic sclerosis can be chemically induced by application of bleomycin or hypochloric acid (HOCl). To date, little is known about inflammatory cells and their potential role in scleroderma (Scl)-related fibrosis. Therefore, we compared both Scl models to define the early immune cell subsets in relation to fibrosis-related parameters. Both agents induced a significant increase in dermal thickness and collagen deposition after 4 weeks, as hallmarks of Scl. However, clinical skin thickness, densely packed, sirius red-stained collagen bundles and collagen cross-links were more pronounced in HOCl-induced Scl. In parallel, there was a significant upregulation of procollagen α1(I), α-SMA and TGF-β transcripts in HOCl animals, whereas IL-1β and MMP-13 mRNA levels were significantly increased in bleomycin-treated mice. Flow cytometric analysis of the Scl skin demonstrated an early cellular infiltrate containing mainly CD19 B cells, CD4 T cells, CD11c DC and CD11b myeloid cells, the latter ones being significantly more prominent after HOCl injection. Subanalysis revealed that Scl mice exhibited a significant increase of inflammatory myeloid CD11b Ly6C CD64 cells (HOCl>bleomycin). In particular, in the HOCl model, activated dermal macrophages (CCR2 MHCII ) and monocyte-derived DC (CCR2 MHCII ) predominated over less activated CD11b myeloid cells. In conclusion, the two models differ in certain aspects of the murine and human scleroderma but in the HOCl model, myeloid CD11b MHCII cells correlate with some fibrosis-related parameters. Therefore, analysis of both models is suggested to cover a comprehensive profile of Scl symptoms but with focus on the HOCl model when the role of early myeloid immune cells will be evaluated.

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Section: Discussionmentioning

confidence: 79%

Myeloid cell populations and fibrogenic parameters in bleomycin‐ and HOCl‐induced fibrosis

Raker

Ook

Haub

et al. 2016

Experimental Dermatology

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“…A previous study (Bourji et al, 2015) reported increased ROS levels in the skin of patients with scleroderma. Exogenous H 2 O 2 increases TGF-b1 and COL1 levels in fibroblasts (Guo et al, 2014;Montorfano et al, 2014), and AQP3 regulates transmembrane H 2 O 2 transportation.…”

Section: Discussionmentioning

confidence: 85%

Activation of TGF-β1 by AQP3-Mediated H2O2 Transport into Fibroblasts of a Bleomycin-Induced Mouse Model of Scleroderma

Luo

Liu

et al. 2016

Journal of Investigative Dermatology

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Hydrogen peroxide (HO), the most important reactive oxygen species, mediates intracellular signal transmission and is transported into cells by aquaporin 3 (AQP3). However, it remains unclear whether AQP3 is involved in the pathogenesis of scleroderma. In this study, we examined the role of AQP3 in a bleomycin-induced mouse model of scleroderma. We observed that HO and AQP3 levels in mouse skin increased with the bleomycin injection period relative to phosphate-buffered saline-injected control mice. AQP3 mRNA and protein levels were higher in bleomycin mice fibroblasts than in phosphate-buffered saline mice fibroblasts, and AQP3 immunofluorescence signals in the cytoplasm and cell membrane of bleomycin mice fibroblasts were much stronger than those in phosphate-buffered saline mice fibroblasts. Bleomycin-induced increases in HO, transforming growth factor-β1, collagen type I, and collagen type III levels in bleomycin mice fibroblasts were blocked by silencing AQP3. In addition, silencing AQP3 decreased HO levels, transforming growth factor-β1 expression, and fibrosis in the scleroderma mouse model. These results demonstrate that AQP3-mediated transport of HO into bleomycin mice fibroblasts activated transforming growth factor-β1, and silencing AQP3 is a potential approach for treating scleroderma.

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“…The total antioxidant capacity (TAC), which accounts for the ability of tissues to counteract oxidative stress, has been reported to be decreased in plasma of SSc patients . The plasma components responsible for the antioxidant status are albumin, uric acid, ascorbic acid, α‐tocopherol, β‐carotene, bilirubin, glutathione, cysteine, dihydrolipoate and ubiquinol.…”

Section: Plasma Antioxidant Capacity In Sscmentioning

confidence: 99%

“…The total antioxidant capacity (TAC), which accounts for the ability of tissues to counteract oxidative stress, has been reported to be decreased in plasma of SSc patients. 14 8…”

mentioning

confidence: 99%

Oxidative stress in the pathogenesis of systemic scleroderma: An overview

Vona¹,

Giovannetti

Gambardella³

et al. 2018

J Cellular Molecular Medi

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Systemic sclerosis (SSc) is a rare disorder of the connective tissue characterized by fibrosis of the skin, skeletal muscles and visceral organs. Additional manifestations include activation of the immune system and vascular injury. SSc causes disability and death as the result of end‐stage organ failure. Two clinical subsets of the SSc are accepted: limited cutaneous SSc (lc‐SSc) and diffuse cutaneous SSc (dc‐SSc). At present, the aetiology and pathogenesis of SSc remain obscure, and consequently, disease outcome is unpredictable. Numerous studies suggest that reactive oxidizing species (ROS) play an important role in the pathogenesis of scleroderma. Over the years, several reports have supported this hypothesis for both lc‐SSc and dc‐SSc, although the specific role of oxidative stress in the pathogenesis of vascular injury and fibrosis remains to be clarified. The aim of the present review was to report and comment the recent findings regarding the involvement and role of oxidative stress in SSc pathogenesis. Biomarkers proving the link between ROS and the main pathological features of SSc have been summarized.

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High reactive oxygen species in fibrotic and nonfibrotic skin of patients with diffuse cutaneous systemic sclerosis

Cited by 43 publications

References 31 publications

Myeloid cell populations and fibrogenic parameters in bleomycin‐ and HOCl‐induced fibrosis

Myeloid cell populations and fibrogenic parameters in bleomycin‐ and HOCl‐induced fibrosis

Activation of TGF-β1 by AQP3-Mediated H2O2 Transport into Fibroblasts of a Bleomycin-Induced Mouse Model of Scleroderma

Oxidative stress in the pathogenesis of systemic scleroderma: An overview

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