Autoimmune mechanisms of scleroderma and a role of oxidative stress

Yamamoto, Toshiyuki

doi:10.4161/self.2.1.14058

Cited by 24 publications

(20 citation statements)

References 76 publications

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“…Oxidative stress, a state of excessive ROS production, may contribute to the pathogenesis of scleroderma [29,34,117,118]. The source of oxidative stress in scleroderma is attributed to ROS production by fibroblasts and activated leukocytes via Nox enzymes [29].…”

Section: The Role Of Nox In Skin Fibrosismentioning

confidence: 99%

NADPH oxidase enzymes in skin fibrosis: molecular targets and therapeutic agents

et al. 2013

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Fibrosis is characterized by the excessive deposition of extracellular matrix components eventually resulting in organ dysfunction and failure. In dermatology, fibrosis is the hallmark component of many skin diseases, including systemic sclerosis, graft versus host disease, hypertrophic scars, keloids, nephrogenic systemic fibrosis, porphyria cutanea tarda, restrictive dermopathy and other conditions. Fibrotic skin disorders may be debilitating and impair quality of life. There are few FDA-approved anti-fibrotic drugs; thus, research in this area is crucial in addressing this deficiency. Recent investigations elucidating the pathogenesis of skin fibrosis have implicated endogenous reactive oxygen species produced by the multicomponent nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) enzyme complex. In this review we discuss Nox enzymes and their role in skin fibrosis. An overview of the Nox enzyme family is presented and their role in the pathogenesis of skin fibrosis is discussed. The mechanisms that Nox enzymes influence specific skin fibrotic disorders are also reviewed. Finally, we describe the therapeutic approaches to ameliorate skin fibrosis by directly targeting Nox enzymes with the use of statins, p47phox subunit modulators, or GKT137831, a competitive inhibitor of Nox enzymes. Nox enzymes can also be targeted indirectly via scavenging ROS with antioxidants. We believe that Nox modulators are worthy of further investigation and have the potential to transform the management of skin fibrosis by dermatologists.

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Section: The Role Of Nox In Skin Fibrosismentioning

confidence: 99%

NADPH oxidase enzymes in skin fibrosis: molecular targets and therapeutic agents

et al. 2013

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“…Our case developed myxoid cyst on the finger, suggesting that mechanical stimuli induced inflammatory cytokines such as IL-1 and IL-6 which exerted effects on activated scleroderma fibroblasts. Further, oxidant stress plays an important role in SSc [5], and low oxygen tension contributes to the increased fibrogenic properties of scleroderma fibroblasts, such as proliferation and collagen production [6,7]. A recent report suggests that hypoxia may play a role in the induction of dermal mucin deposition [8].…”

Section: Discussionmentioning

confidence: 99%

Cutaneous myxoid cyst on the sclerotic finger in a patient with diffuse systemic sclerosis

Nakamura-Wakatsuki¹,

Yamamoto

2013

Our Dermatol Online

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Skin tumors occurring on the scleroderma fingers are rarely seen. Swollen fingers are hallmarks of systemic sclerosis, and mucin deposition in the lesional skin is a constant feature in systemic sclerosis. Here we describe a case of cutaneous myxoid cyst on the flexor aspect of the sclerotic fingers in a patient with severe diffuse cutaneous systemic sclerosis. Cutaneous myxoid cyst is a relatively common benign tumor; however, cases of cutaneous myxoid cysts developing on the scleroderma fingers have not been reported to date. Mucin deposition in the sclerotic skin may be a predisposing factor in the induction of myxoid cyst on the scleroderma finger in our patient.

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“…Reactive oxygen species (ROS) are involved in the pathogenesis of SSc [89]. Serum levels of DNA oxidative markers are significantly elevated in patients with SSc, with a relevant association with a fibrotic phenotype [90].…”

Section: Oxidative Stressmentioning

confidence: 99%

Updates on the pathophysiology of dermal sclerosis

Yamamoto¹

2012

Expert Review of Dermatology

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Autoimmune mechanisms of scleroderma and a role of oxidative stress

Abstract: To cite this article: Toshiyuki Yamamoto (2011) Autoimmune mechanisms of scleroderma and a role of oxidative stress, Self/Nonself, 2:1, 4-10,

Cited by 24 publications

References 76 publications

NADPH oxidase enzymes in skin fibrosis: molecular targets and therapeutic agents

NADPH oxidase enzymes in skin fibrosis: molecular targets and therapeutic agents

Cutaneous myxoid cyst on the sclerotic finger in a patient with diffuse systemic sclerosis

Updates on the pathophysiology of dermal sclerosis

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