The mechanism of hyperpigmentation in seborrhoeic keratosis involves the high expression of endothelin-converting enzyme-1alpha and TNF-alpha, which stimulate secretion of endothelin 1

Manaka, Izumi; Kadono, Satsuki; Kawashima, Makoto; Kobayashi, Takashi; Imokawa, Genji

doi:10.1046/j.1365-2133.2001.04521.x

Cited by 48 publications

(50 citation statements)

References 16 publications

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“…When SP binds to NK1R, SP-NK1R-b-arrestin forms a signalosome and is endocytosed with ECE1 on the cell surface, generating an early endosome in which ECE1 disrupts the SP-NK1R complex potentially by degrading SP and inducing NK1R recycling to the plasma membrane (Roosterman et al, 2007;Pelayo et al, 2011). In addition to the role of ECE1 as a regulator of the endocytic signaling of SP-NK1R, ECE1 is a known key enzyme that mediates melanogenesis by catalyzing the specific cleavage of inactive Big-EDN1 to produce an active EDN1 in keratinocytes and endothelial cells (Yanagisawa et al, 1988;Kido et al, 1997), as demonstrated by the increased level of secreted EDN1 in several hyperpigmented lesions (Manaka et al, 2001). ECE1 regulates the endocytic signaling and trafficking of SP1-NK1R and activates EDN1 via direct cleavage; therefore, we initially hypothesized that SP-NK1R-dependent endocytosed ECE1 interacts with and cleaves the inactive Big-EDN1 residing within vesicles in the secretory pathway in human melanocytes.…”

Section: Discussionmentioning

confidence: 96%

Substance P Stimulates Endothelin 1 Secretion via Endothelin-Converting Enzyme 1 and Promotes Melanogenesis in Human Melanocytes

Park

Lee

Cho

2015

Journal of Investigative Dermatology

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Substance P (SP) is a well-known neuropeptide implicated in the wound-healing process. The wound occasionally causes a pigmented scar. In the present study, we examined whether increased levels of SP affected melanogenesis. When human melanocytes were treated with SP, the melanin content increased and the pigmentation process accelerated in a dose-dependent manner. In addition to melanogenesis-related genes, the expression of neurokinin 1 receptor, endothelin 1 (EDN1), and EDN receptor type B (EDNRB) also increased at both the messenger RNA and protein levels. Interestingly, secreted EDN1 was observed in the melanocyte culture medium, and this phenomenon was significantly enhanced by SP treatment. Through knockdown experiments using small interfering RNAs (siRNAs), we confirmed that endothelin-converting enzyme 1 (ECE1), EDN1, and EDNRB were involved in SP-induced pigmentation and found that EDN1 secretion was affected by ECE1 and EDN1 siRNAs, but not by EDNRB siRNA. These findings indicate that ECE1 is essential for EDN1 secretion in melanocytes and that EDNRB functions downstream of secreted EDN1 to increase the cAMP levels and activate the melanogenesis-related phosphorylation cascade. This study provides in vitro evidence for a melanogenic function of SP in the skin and suggests that the SP-related signal is a potent target for regulating stress- or wound-induced pigmentation.

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Section: Discussionmentioning

confidence: 96%

Substance P Stimulates Endothelin 1 Secretion via Endothelin-Converting Enzyme 1 and Promotes Melanogenesis in Human Melanocytes

Park

Lee

Cho

2015

Journal of Investigative Dermatology

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“…It is commonly that UV-induced hyperpigmentation is composed of three major steps: the first step is the proliferation of melanocytes (5), followed by increased melanogenesis, and ultimately, the transfer of melanosomes from melanocytes to keratinocytes (6,7). In recent years, the relationships between endothelins and pigment diseases have drawn considerable attention due to the indispensable role of endothelins in epidermal pigmentation in several hyperpigmentary disorders (8,9). As intrinsic mediators for human melanocytes, endothelins play vital roles in UVB-induced pigmentation (8).…”

Section: Introductionmentioning

confidence: 99%

“…ET-1 was firstly isolated from vascular endothelial cells (10), and can induce mitogenesis and melanogenesis in primary human melanocytes (11). The increased secretion of ET-1 is intrinsically considered to be involved in the hyperpigmentation mechanism of SK (9,12). However, the precise mechanisms involved in this process are lacking.…”

Section: Introductionmentioning

confidence: 99%

Endothelin-1 enhances the melanogenesis via MITF-GPNMB pathway

Zhang¹,

Liu²,

Yuan³

et al. 2013

BMB Reports

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Endothelin-1 (ET-1) plays an indispensable role in epidermal pigmentation in hyperpigmentary disorders due to a central role in melanogenesis. Nevertheless, precise mechanism involved in ET-1-induced hyperpigmentation is still undefined. Glycoprotein (transmembrane) non-metastatic melanoma protein b (GPNMB) is a key element in melanosome formation. Therefore, we speculated that GPNMB was correlated with ET-1-induced pigmentation. After culturing with ET-1, melanin synthesis was significantly up-regulated, accompanying with increased expression of GPNMB and microphthalmia-associated transcription factor (MITF). Total number of melanosomes and melanin synthesis were sharply reduced via GPNMB-siRNA transfection, indicating ET-1-induced pigmentation by GPNMB-dependent manner. Furthermore, MITFsiRNA transfection strikingly inhibited GPNMB expression and the melanogenesis, and this suppression failed to be alleviated by ET-1 stimulation. All of these results demonstrated that ET-1 can trigger melanogenesis via the MITF-regulated GPNMB pathway. Taken together, these findings will provide a new explanation of how ET-1 induces hyperpigmentation, and possibly supply a new strategy for cosmetic studies. [BMB Reports 2013; 46(7): 364-369]

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“…The hyperpigmentation may be due to expression of endothelin‐1, a peptide that triggers melanocyte activation . This is the same peptide that has been implicated to partake in the pigmentation process of seborrheic keratosis, actinic keratosis, and basal cell carcinoma …”

Section: Introductionmentioning

confidence: 99%

Eccrine poromatosis: case report and review of the literature

et al. 2013

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Eccrine poroma (EP) is a benign tumor of the eccrine duct. Multiple EPs are defined as eccrine poromatosis (EPS), an uncommon phenomenon. To date there are only eight reported cases of EPS. This review exemplifies the epidemiology, pathogenesis, differential diagnosis, and histology of EP, while reviewing the eight cases of EPS. Six of the eight cases of EPS had a history of immunosuppression from either radiation or chemotherapy. This paper will also emphasize the importance of excision to avoid possible malignancy. Here we present a 73-year-old gentleman with EPS who was also treated with radiation and chemotherapy prior to the onset of the lesions.

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The mechanism of hyperpigmentation in seborrhoeic keratosis involves the high expression of endothelin-converting enzyme-1alpha and TNF-alpha, which stimulate secretion of endothelin 1

Abstract: These findings suggest that the increased secretion of ET-1 leading to enhanced pigmentation in SK results from the co-ordinated increased expression of TNF-alpha and ECE-1alpha.

Cited by 48 publications

References 16 publications

Substance P Stimulates Endothelin 1 Secretion via Endothelin-Converting Enzyme 1 and Promotes Melanogenesis in Human Melanocytes

Substance P Stimulates Endothelin 1 Secretion via Endothelin-Converting Enzyme 1 and Promotes Melanogenesis in Human Melanocytes

Endothelin-1 enhances the melanogenesis via MITF-GPNMB pathway

Eccrine poromatosis: case report and review of the literature

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