Messenger RNA levels of melanogenesis-associated genes in lentigo senilis lesions

Motokawa, Tomonori; Kato, Tomomi; Katagiri, Takayuki; Matsunaga, Jun; Takeuchi, Izuho; Tomita, Yasushi; Suzuki, Itaru

doi:10.1016/j.jdermsci.2004.10.009

Cited by 26 publications

(15 citation statements)

References 5 publications

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“…SCF, ET-1, and POMC, in the pigmented spots compared with peripheral control areas (Fig. 1C), which is consistent with previous studies (26,27,32). In addition, significantly greater expression of p53 (represented by the blue color) was observed in the nuclei of epidermal keratinocytes in pigmented spots compared with peripheral control areas using immunohistological analysis (Fig.…”

Section: The Expression and Phosphorylation Of P53 Is Stimulated In Hsupporting

confidence: 91%

“…Such evidence indicates that the mechanisms of several types of hyperpigmentation, such as UV-induced pigmentation (suntanning) and senile lentigos, commonly share increased SCF/KIT and ET-1/ET B R signaling and reveals their coordinated roles in regulating epidermal melanogenesis as a part of skin homeostasis consistent with a previous study (31). Additionally, Motokawa et al (32) reported that expression of the POMC (pro-opiomelanocortin) gene, which encodes a precursor of ␣-melanocyte-stimulating hormone, is higher in the epidermis of senile lentigines than in peripheral epidermal controls.…”

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confidence: 83%

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The Essential Role of p53 in Hyperpigmentation of the Skin via Regulation of Paracrine Melanogenic Cytokine Receptor Signaling

Murase

Hachiya

Amano

et al. 2009

Journal of Biological Chemistry

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Hyperpigmentation of the skin is characterized by increases in melanin synthesis and deposition. Although considered a significant psychosocial distress, little is known about the detailed mechanisms of hyperpigmentation. Recently, the tumor suppressor protein p53 has been demonstrated to promote ultraviolet B-induced skin pigmentation by stimulating the transcription of a melanogenic cytokine, POMC (pro-opiomelanocortin), in keratinocytes. Given that p53 can be activated by various kinds of diverse stresses, including sun exposure, inflammation, and aging, this finding led us to examine the involvement of p53 in cytokine receptor signaling, which might result in skin hyperpigmentation. Immunohistochemical and reverse transcription-PCR analyses revealed the increased expression and phosphorylation of p53 in the epidermis of hyperpigmented spots, accompanied by the higher expression of melanogenic cytokines, including stem cell factor, endothelin-1, and POMC. The involvement of p53 in hyperpigmentation was also indicated by the significantly higher expression of p53 transcriptional targets in the epidermis of hyperpigmented spots. Treatment of human keratinocytes and melanocytes with known p53 activators or inhibitors, including pifithrin-␣ (PFT), demonstrated significant increases or decreases, respectively, in the expression of melanogenic factors, including cytokines and their receptors. Additionally, PFT administration abolished stem cell factor-induced phosphorylation of mitogen-activated protein kinase in human melanocytes. Furthermore, when organ-cultured hyperpigmented spots, in vitro human skin substitutes, and mouse skin were treated with PFT or p53 small interfering RNA, the expression of melanogenic cytokines and their receptors was significantly decreased, as were levels of tyrosinase and melanogenesis. Taken together, these data reveal the essential role of p53 in hyperpigmentation of the skin via the regulation of paracrine-cytokine signaling, both in keratinocytes and in melanocytes.There are various types of hyperpigmentations (pigmented spots) of the skin characterized by increases in melanin synthesis and deposition, such as freckles, postinflammatory hyperpigmentation, UV-induced pigmentation (UV-melanoses), senile lentigines (age spots), pigmentation petaloides actinica, and melasma. These hyperpigmentations are well known to cause significant psychosocial distress, but little is known about their detailed mechanisms.Hyperpigmentation generally results from three major steps in the epidermis: the proliferation of melanocytes, the synthesis and activation of tyrosinase to produce melanin, and the transfer of melanosomes to keratinocytes (1-4). During the first two steps, a complicated network composed of paracrine and autocrine cytokines secreted by keratinocytes and by melanocytes, respectively, plays an important role in regulating melanogenesis in collaboration with their corresponding receptors, whose expression is also regulated by various cytokines (5-23). In addition, several types of c...

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Section: The Expression and Phosphorylation Of P53 Is Stimulated In Hsupporting

confidence: 91%

supporting

confidence: 83%

The Essential Role of p53 in Hyperpigmentation of the Skin via Regulation of Paracrine Melanogenic Cytokine Receptor Signaling

Murase

Hachiya

Amano

et al. 2009

Journal of Biological Chemistry

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“…This is supported by molecular data showing that levels of melanocyte‐ or melanogenesis‐related genes are not significantly altered in lesional skin compared with adjacent NL skin. This is a particularly striking result as most previous studies have reported an upregulation of genes or proteins involved in melanin synthesis, melanosome biogenesis or melanogenesis regulation in AL . Overall, our results suggest normal melanocyte homeostasis within the lesions selected for this study.…”

Section: Discussionsupporting

confidence: 75%

Morphological and molecular characterization of actinic lentigos reveals alterations of the dermal extracellular matrix

et al. 2017

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“…SL samples were reported to have unchanged (6) or slightly increased (3,4,9) melanocyte number. Pigmentary proteins like tyrosinase (TYR), TYR-related protein-1, dopachrome tautomerase, Pmel-17, proopiomelanocortin (3,10), endothelin-1, endothelin receptor B and stem cell factor and its receptor (c-KIT) (11,12) are all increased in SL lesions. Pigmentary proteins like tyrosinase (TYR), TYR-related protein-1, dopachrome tautomerase, Pmel-17, proopiomelanocortin (3,10), endothelin-1, endothelin receptor B and stem cell factor and its receptor (c-KIT) (11,12) are all increased in SL lesions.…”

Section: Introductionmentioning

confidence: 99%

“…The expression of Ki67, a proliferation marker, was reported either as unchanged (6) or as reduced (3) in SL lesions. Pigmentary proteins like tyrosinase (TYR), TYR-related protein-1, dopachrome tautomerase, Pmel-17, proopiomelanocortin (3,10), endothelin-1, endothelin receptor B and stem cell factor and its receptor (c-KIT) (11,12) are all increased in SL lesions. Additionally, genetic studies suggest that several melanocortin receptor-1 variants are linked to SL susceptibility (13,14).…”

Section: Introductionmentioning

confidence: 99%

The role of keratinocyte growth factor in melanogenesis: a possible mechanism for the initiation of solar lentigines

Chen

et al. 2009

Experimental Dermatology

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Solar lentigines (SLs) are hyperpigmentary lesions presented on sun-exposed areas of the skin and associated with ageing. The molecular mechanism of SL initiation is not completely understood. Ultraviolet B (UVB) stimulates keratinocytes to produce interlukin-1 alpha (IL-1α), which then induces keratinocyte growth factor (KGF) secretion; therefore, we examined their possible roles in the induction of SLs. We found that KGF increases pigment production in both pigmented epidermal equivalents and human skin explants. In addition, UVB exposure increases KGF expression, and KGF treatment induces tyrosinase (TYR) expression in primary melanocytes. The KGF-induced pigmentary changes were confirmed using pigmented Yucatan swine, and human skins grafted onto immuno-deficient mice. In both model systems, the topical treatment with KGF, alone or in combination with IL-1α, resulted in the in vivo formation of hyperpigmentary lesions with increased pigment deposition and elongated rete ridges, which resemble the histological features of human SLs. Preliminary immunohistochemical analysis of human skins showed a moderate increase in KGF, and a strong induction in KGF receptor (KGFR) in SL lesions. In summary, KGF increases pigment production and deposition in vitro and in vivo. Moreover, we show for the first time the in vivo generation of hyperpigmentary lesions with histological resemblance to human SLs and indicate the involvement of KGF/KGFR in the molecular pathology of human SLs.

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Messenger RNA levels of melanogenesis-associated genes in lentigo senilis lesions

Cited by 26 publications

References 5 publications

The Essential Role of p53 in Hyperpigmentation of the Skin via Regulation of Paracrine Melanogenic Cytokine Receptor Signaling

The Essential Role of p53 in Hyperpigmentation of the Skin via Regulation of Paracrine Melanogenic Cytokine Receptor Signaling

Morphological and molecular characterization of actinic lentigos reveals alterations of the dermal extracellular matrix

The role of keratinocyte growth factor in melanogenesis: a possible mechanism for the initiation of solar lentigines

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