Impact of high-mobility group box 1 on melanocytic survival and its involvement in the pathogenesis of vitiligo

Kim, J.Y.; Lee, Eun Jung; Seo, Jeong Taeg; Oh, Sang Ho

doi:10.1111/bjd.15151

Cited by 36 publications

(31 citation statements)

References 52 publications

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“…This confirmed the role of autocrine HMGB1 in the expression of Nrf2 and its downstream genes. Kim et al have reported that recombinant HMGB1 protein induced by external stimuli led to melanocyte apoptosis. The HMGB1 used in their experiments was exogenous recombinant HMGB1, which does not reflect the role of HMGB1 in melanocytes.…”

Section: Discussionsupporting

confidence: 85%

“…These data showed that oxidative stress may be a common mechanism for regulating the translocation, release and activity of HMGB1, including in NHEMs. A couple of reports have demonstrated that HMGB1 is expressed in keratinocytes and released from them under ultraviolet radiation or H 2 O 2 treatment. As shown in Figures and , HMGB1 is mainly expressed in the nucleus of NHEMs and is translocated from the nucleus to the cytoplasm after exposure to low doses of H 2 O 2 .…”

Section: Discussionmentioning

confidence: 99%

“…Recently, Kim et al have suggested a potential role for HMGB1 from keratinocytes in melanogenesis and demonstrated that secretion of HMGB1 from neighbouring keratinocytes influences melanocyte survival and the expression of melanogenesis‐related molecules. It is not clear whether the melanocytes themselves produce HMGB1.…”

Section: Introductionmentioning

confidence: 99%

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HMGB1 deficiency reduces H₂O₂‐induced oxidative damage in human melanocytes via the Nrf2 pathway

Mou

Liu

Miao

et al. 2018

J Cellular Molecular Medi

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Oxidative stress leads to melanocyte death and has been implicated in the pathogenesis of vitiligo. The nuclear factor, E2‐related factor 2 (Nrf2), is a critical transcription factor in protecting cells from oxidative damage. High‐mobility group box 1 (HMGB1) is a chromatin‐associated nuclear protein and an extracellular damage‐associated molecular pattern molecule. Extracellular HMGB1 released from activated immune cells, necrotic or injured cells, becomes a proinflammatory mediator through binding to cell‐surface receptors of responding cells. In this study, we investigated the role of HMGB1 from melanocytes in the response to oxidative stress and the mechanism involved. We showed that HMGB1 is expressed by primary normal human epidermal melanocytes (NHEMs). H2O2 treatment increased cytoplasmic translocation and extracellular release of HMGB1. HMGB1 knockdown by small interfering RNA (siRNA) led to decreased apoptosis of NHEMs. HMGB1 inhibition enhanced the expression of Nrf2 and its target genes. The expression of Nrf2 and its downstream antioxidant genes was downregulated after the supernatant of H2O2‐treated NHEMs was added to HMGB1‐deficient cells. HMGB1 knockdown by siRNA suppressed the expression of the autophagosome marker, LC3, and enhanced p62 expression. Coimmunoprecipitation with Keap1 showed a reduced Nrf2‐Keap1 interaction and an increased p62‐Keap1 interaction under oxidative stress. These data demonstrated that external stimuli (eg, oxidative stress) may trigger autocrine HMGB1 translocation and release by melanocytes, suppressing the expression of Nrf2 and downstream antioxidant genes to induce melanocyte apoptosis, and thereby participate in the pathological process of vitiligo.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

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HMGB1 deficiency reduces H₂O₂‐induced oxidative damage in human melanocytes via the Nrf2 pathway

Mou

Liu

Miao

et al. 2018

J Cellular Molecular Medi

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“…Here, Kim et al . suggest the potential role of HMGB1 from keratinocytes in melanogenesis and demonstrate that secretion of HMGB1 from neighbouring keratinocytes influences melanocyte survival and the expression of melanogenesis‐related molecules.…”

mentioning

confidence: 79%

“…This issue of the BJD includes an interesting piece of research by Kim and coworkers outlining a possible association between high‐mobility group box 1 (HMGB1) and vitiligo. HMGB1 is a DNA‐binding nonhistone protein that acts as a transcriptional regulator participating in DNA replication, recombination, transcription and repair.…”

mentioning

confidence: 99%

Oxidative stress and high-mobility group box 1 (HMGB1) protein release in vitiligo

Becatti

2017

Br J Dermatol

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Mechanisms of melanocyte death in vitiligo

Chen

2020

Medicinal Research Reviews

161

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Vitiligo is an autoimmune depigment disease results from extensive melanocytes destruction. The destruction of melanocyte is thought to be of multifactorial causation. Genome‐wide associated studies have identified single‐nucleotide polymorphisms in a panel of susceptible loci as risk factors in melanocyte death. But vitiligo onset can't be solely attributed to a susceptive genetic background. Oxidative stress triggered by elevated levels of reactive oxygen species accounts for melanocytic molecular and organelle dysfunction, a minority of melanocyte demise, and melanocyte‐specific antigens exposure. Of note, the self‐responsive immune function directly contributes to the bulk of melanocyte deaths in vitiligo. The aberrantly heightened innate immunity, type‐1‐skewed T helper, and incompetent regulatory T cells tip the balance toward autoreaction and CD8+ cytotoxic T lymphocytes finally execute the killing of melanocytes, possibly alarmed by resident memory T cells. In addition to the well‐established apoptosis and necrosis, we discuss several death modalities like oxeiptosis, ferroptosis, and necroptosis that are probably employed in melanocyte destruction. This review focuses on the various mechanisms of melanocytic death in vitiligo pathogenesis to demonstrate a panorama of that. We hope to provide new insights into vitiligo pathogenesis and treatment strategies by the review.

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Impact of high-mobility group box 1 on melanocytic survival and its involvement in the pathogenesis of vitiligo

Abstract: External stimuli (e.g. oxidative stress and ultraviolet irradiation) may trigger HMGB1 release by keratinocytes, thereby perpetuating vitiligo through HMGB1-induced melanocytic apoptosis.

Cited by 36 publications

References 52 publications

HMGB1 deficiency reduces H₂O₂‐induced oxidative damage in human melanocytes via the Nrf2 pathway

HMGB1 deficiency reduces H₂O₂‐induced oxidative damage in human melanocytes via the Nrf2 pathway

Oxidative stress and high-mobility group box 1 (HMGB1) protein release in vitiligo

Mechanisms of melanocyte death in vitiligo

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Impact of high-mobility group box 1 on melanocytic survival and its involvement in the pathogenesis of vitiligo

Abstract: External stimuli (e.g. oxidative stress and ultraviolet irradiation) may trigger HMGB1 release by keratinocytes, thereby perpetuating vitiligo through HMGB1-induced melanocytic apoptosis.

Cited by 36 publications

References 52 publications

HMGB1 deficiency reduces H2O2‐induced oxidative damage in human melanocytes via the Nrf2 pathway

HMGB1 deficiency reduces H2O2‐induced oxidative damage in human melanocytes via the Nrf2 pathway

Oxidative stress and high-mobility group box 1 (HMGB1) protein release in vitiligo

Mechanisms of melanocyte death in vitiligo

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HMGB1 deficiency reduces H₂O₂‐induced oxidative damage in human melanocytes via the Nrf2 pathway

HMGB1 deficiency reduces H₂O₂‐induced oxidative damage in human melanocytes via the Nrf2 pathway