Melanocyte detachment after skin friction in non lesional skin of patients with generalized vitiligo

Gauthier, Yvon; Cario‐André, Muriel; Lepreux, Sébastien; Pain, Catherine; Taı̈eb, Alain

doi:10.1046/j.1365-2133.2003.05024.x

Cited by 160 publications

(120 citation statements)

References 49 publications

(46 reference statements)

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“…Melanocytes and keratinocytes seem to exhibit a functionally and structurally close relationship to a great extent that is mediated by keratinocyte-derived cytokines. Gauthier et al (2003) described the presence of a large extracellular space between the melanocytes, vacuoles in keratinocytes containing tenascin, which can promote the extracellular detachment of melanocytes. Moreover, keratinocytes produce and release high amounts of proinflammatory cytokines including TNF-α, which promotes the expression of adhesion molecules on the melanocyte membrane (intercellular adhesion molecule 1), leading to further lymphocyte recruitment.…”

Section: Discussionmentioning

confidence: 99%

Tumor necrosis factor-α and -β genetic polymorphisms as a risk factor in Saudi patients with vitiligo

Al-Harthi

Zouman²,

Arfin³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. Vitiligo is an acquired depigmentary disorder of the skin, characterized by multiple susceptibility loci and genetic heterogeneity. The etiology of vitiligo is unknown but several hypotheses, including an autoimmune origin, have been proposed. Tumor necrosis factor (TNF)-α, a pleiotropic proinflammatory cytokine, has been shown to play a critical role in several autoimmune diseases including vitiligo. The aim of present study was to determine the association of TNF-α and -β gene polymorphisms with vitiligo in Saudi patients. TNF-α and -β genes were amplified in 123 Saudi patients and 200 matched controls using polymerase chain reaction to search for polymorphisms involved at positions -308, and intron 1 +252. The frequency of the TNF-α (-308) GA genotype was higher and the frequencies of the GG and AA genotypes were significantly lower in vitiligo patients compared to controls. These findings suggested that genotype GA-positive individuals at position -308 of TNF-α are susceptible to vitiligo, whereas the GG and AA genotypes might exert a protective effect. The frequency of allele A (TNF-α 2-allele) was significantly higher and that of allele G (TNF-α 1-allele) was lower in vitiligo patients compared to controls, indicating an association of allele A with susceptibility to TNF-α and -β polymorphisms in vitiligo vitiligo in Saudi patients. The results of our examination of TNF-β (intron 1 +252) polymorphisms showed a significant increase in the frequency of the GG genotype and allele G (TNF-b 1-allele) in vitiligo patients, suggesting a susceptibility of the GG genotype and allele G for vitiligo. By contrast, the high frequency of the GA genotype in controls might indicate a protective effect. The results of the present study strongly support a link between TNF-α (-308) and -β (intron 1 +252) polymorphisms and vitiligo in Saudi patients.

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Section: Discussionmentioning

confidence: 99%

Tumor necrosis factor-α and -β genetic polymorphisms as a risk factor in Saudi patients with vitiligo

Al-Harthi

Zouman²,

Arfin³

et al. 2013

Genet. Mol. Res.

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“…The detachment of living melanocytes after friction of perilesional NSV skin has been observed recently. Melanocyte detachment from the basal layer was followed by transepidermal migration and eventually the death of pigment cells (4).…”

Section: Introductionmentioning

confidence: 99%

A Critical Appraisal of Vitiligo Etiologic Theories. Is Melanocyte Loss a Melanocytorrhagy?

Gauthier

andre

Taı̈eb

2003

Pigment Cell Research

264

211

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Common generalized vitiligo is an acquired depigmenting disorder characterized by a chronic and progressive loss of melanocytes from the epidermis and follicular reservoir. However, the mechanism of melanocyte disappearance has never been clearly understood, and the intervention of cellular and humoral autoimmune phenomena as primary events remains unproven. In this review, is discussed the data supporting the major theories of vitiligo, namely melanocyte destruction (autoimmune, neural and impaired redox status) and melanocyte inhibition or defective adhesion. Based on recent morphologic findings in vivo supporting a chronic detachment and transepidermal loss of melanocytes in common generalized vitiligo, a new theory is suggested proposing melanocytorrhagy as the primary defect underlying melanocyte loss, integrating most of the possible triggering/precipitating/ enhancing effects of other known factors.

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“…1 Characterized by patchy depigmentation of the skin, the disease can affect the patients' self-image, or even cause depression, thus substantially decreasing life quality among vitiligo patients. 2 Although several etiological theories, including genetic predisposition, [3][4][5] autoimmunity, 6,7 melanocytorrhagy 8,9 and toxic metabolites 10 have been proposed to participate in the pathogenesis of vitiligo, the exact mechanism of melanocyte degeneration in depigmented lesions still remains unclear.…”

mentioning

confidence: 99%

Oxidative stress-induced overexpression of miR-25: the mechanism underlying the degeneration of melanocytes in vitiligo

et al. 2015

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Oxidative stress has a critical role in the pathogenesis of vitiligo. However, the specific molecular mechanism involved in oxidative stress-induced melanocyte death is not well characterized. Given the powerful role of microRNAs (miRNAs) in the regulation of cell survival as well as the fact that the generation of miRNAs can be affected by oxidative stress, we hypothesized that miRNAs may participate in vitiligo pathogenesis by modulating the expression of vital genes in melanocytes. In the present study, we initially found that miR-25 was increased in both serum and lesion samples from vitiligo patients, and its serum level was correlated with the activity of vitiligo. Moreover, restoration of miR-25 promoted the H 2 O 2 -induced melanocyte destruction and led to the dysfunction of melanocytes. Further experiments proved that MITF, a master regulator in melanocyte survival and function, accounted for the miR-25-caused damaging impact on melanocytes. Notably, other than the direct role on melanocytes, we observed that miR-25 inhibited the production and secretion of SCF and bFGF from keratinocytes, thus impairing their paracrine protective effect on the survival of melanocytes under oxidative stress. At last, we verified that oxidative stress could induce the overexpression of miR-25 in both melanocytes and keratinocytes possibly by demethylating the promoter region of miR-25. Taken together, our study demonstrates that oxidative stress-induced overexpression of miR-25 in vitiligo has a crucial role in promoting the degeneration of melanocytes by not only suppressing MITF in melanocytes but also impairing the paracrine protective effect of keratinocytes. Therefore, it is worthy to investigate the possibility of miR-25 as a potential drug target for anti-oxidative therapy in vitiligo. Vitiligo is a disfiguring dermatosis with an incidence rate of approximately 0.5-1.0% in the populations worldwide. 1 Characterized by patchy depigmentation of the skin, the disease can affect the patients' self-image, or even cause depression, thus substantially decreasing life quality among vitiligo patients. 2 Although several etiological theories, including genetic predisposition, 3-5 autoimmunity, 6,7 melanocytorrhagy 8,9 and toxic metabolites 10 have been proposed to participate in the pathogenesis of vitiligo, the exact mechanism of melanocyte degeneration in depigmented lesions still remains unclear.The generation of oxidative stress has long been demonstrated to have a crucial role in the onset and progression of vitiligo. 11,12 Owing to the pro-oxidant state generated during melanin synthesis, melanocytes are particularly vulnerable to oxidative stress. 13 In vitiligo, accumulation of toxic intermediates such as 6-and 7-BH4 and catecholamine, 14,15 concomitant with reduced levels and activity of catalase and several other antioxidant enzymes [16][17][18] have been demonstrated in patients' epidermis. Because of these intracellular metabolic disorder and compromised intrinsic antioxidant defenses, hydrogen peroxide (H 2 O ...

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Melanocyte detachment after skin friction in non lesional skin of patients with generalized vitiligo

Cited by 160 publications

References 49 publications

Tumor necrosis factor-α and -β genetic polymorphisms as a risk factor in Saudi patients with vitiligo

Tumor necrosis factor-α and -β genetic polymorphisms as a risk factor in Saudi patients with vitiligo

A Critical Appraisal of Vitiligo Etiologic Theories. Is Melanocyte Loss a Melanocytorrhagy?

Oxidative stress-induced overexpression of miR-25: the mechanism underlying the degeneration of melanocytes in vitiligo

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