endothelin-1 and Melanosis

Riehl's melanosis is a hyperpigmentary disorder that occurs predominantly on the face and neck. To date, the pathogenesis of Riehl's melanosis with regards to the melanogenic properties and paracrine melanogenic molecules has not well been studied. This study was aimed to provide a novel perspective on the pathogenesis of Riehl's melanosis by identifying the relevant paracrine melanogenic molecules in Riehl's melanosis. Skin biopsies were performed on lesional and normal-appearing perilesional skin of 12 patients with Riehl's melanosis and 12 age- and sex-matched healthy controls. Histopathological and immunohistochemical staining for paracrine melanogenic molecules was analyzed. The major histopathological findings of Riehl's melanosis were basal hyperpigmentation, melanocyte proliferation, interface change, dermal pigmentary incontinence, vascular proliferation, and dermal inflammation. Dermal expression intensities of stem cell factor (SCF) and c-kit were increased in the lesional skin of Riehl's melanosis. In addition, increased expression of epidermal and dermal ET-1 was also observed in the lesional skin of Riehl's melanosis. Increased tissue expressions of SCF, c-kit, and ET-1 in Riehl's melanosis support the role of these paracrine melanogenic molecules in the pathogenesis of Riehl's melanosis. The findings from this study might present useful information on the pathogenetic mechanism of Riehl's melanosis.

Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; Case-Control Studies; Endothelin-1; Factor XIIIa; Female; Gene Expression Profiling; Gene Expression Regulation; Humans; Melanins; Melanocytes; Melanosis; Middle Aged; Paracrine Communication; Proto-Oncogene Proteins c-kit; Skin; Stem Cell Factor

Tranexamic acid (TA) has been suggested as an effective treatment for melasma.. To investigate the effects and mechanism of action of topical TA in the treatment of melasma.. In this study, 23 participants with melasma applied a 2% TA formulation to the whole face for 12 weeks. Clinical effects were evaluated using the modified Melasma Area and Severity Index (mMASI) and a chromameter. Skin biopsies were obtained from 10 participants to evaluate pigmentation, vascularity and the expression levels of possible paracrine factors contributing to the effect of TA.. Most of the participants had mild melasma, with mMASI of < 5. The mMASI scores significantly improved in 22 of 23 participants after application. The L* values were increased and the a* values were decreased in both lesional and perilesional normal skin. Fontana-Masson staining showed a significant decrease in melanin content in the epidermis. The number of CD31-positive vessels and the expression of the vascular endothelial growth factor both tended to decrease. Endothelin (ET)-1 was found to be downregulated with TA.. Topical TA is effective for melasma. This immunohistochemical study found that suppression of ET-1 could be one of the mechanisms of action of TA on melasma.

Topics: Adult; Antifibrinolytic Agents; Biomarkers; Endothelin-1; Female; Humans; Immunohistochemistry; Melanosis; Middle Aged; Severity of Illness Index; Tranexamic Acid; Vascular Endothelial Growth Factor A

The aim of this study was to investigate the possible pathological relation between mechanical stress and hyperpigmentation. We did this by investigating the influence of cyclic stretch on the expression of keratinocyte- and fibroblast-derived melanogenetic paracrine cytokines in vitro. Using primary human keratinocytes and fibroblasts, alterations of mRNA expression of melanogenetic paracrine cytokines due to cyclic stretch were investigated using a real-time polymerase chain reaction (PCR). The cytokines included basic fibroblast growth factor (bFGF), stem cell factor (SCF), granulocyte/macrophage colony-stimulating factor, interleukin-1α, and endothelin-1 (ET-1) for keratinocytes and bFGF, SCF, and hepatocyte growth factor for fibroblasts. The dose dependence of keratinocyte-derived ET-1 upregulation was further investigated using real-time PCR and an enzyme-linked immunosorbent assay. We also investigated the effects of cyclic stretch on the proliferation and differentiation of keratinocytes. Among the melanogenetic paracrine cytokines investigated, keratinocyte-derived ET-1 was consistently upregulated in all four cell lines. The degree of upregulation increased with the degree of the length and frequency of the stretch; in contrast, cell number and differentiation markers showed no obvious alterations with cyclic stretch. Keratinocyte-derived ET-1 upregulation possibly plays a significant role in the pathogenesis of pigmented disorders, such as friction melanosis, caused by mechanical stress.

Topics: Cells, Cultured; Endothelin-1; Fibroblasts; Humans; Hyperpigmentation; Keratinocytes; Melanosis; Stress, Mechanical; Up-Regulation

We present here the clinical, morphological and immunohistochemical features of a pigmented squamous cell carcinoma (SCC) in the oral mucosa of the hard palate of a 76-year-old Japanese man. He underwent a partial resection of the maxilla subsequent to radiotherapy. The tumor was typical, moderately well-differentiated SCC but had many melanocytes (melanocytosis) within it. Immunohistochemical analysis for stem cell factor (SCF) and endothelin-1, both of which are known to stimulate proliferation and differentiation of melanocytes, revealed prominent expression of both factors in the neoplastic squamous cells of the pigmented SCC, while the non-pigmented oral SCC showed little sign of either factor. These findings strongly suggest that SCF and endothelin-1 secreted by neoplasmic squamous cells are involved in the emergence of a rare variant of oral SCC.

Topics: Aged; Carcinoma, Squamous Cell; Endothelin-1; Humans; Male; Melanocytes; Melanosis; Palatal Neoplasms; Stem Cell Factor

The origin of diffuse melanosis resulting from metastatic melanoma is unknown. We examined the light microscopic and ultrastructural changes in the skin of an affected 35-year-old woman and determined the peripheral blood levels of melanocyte growth factors. A total of 7 biopsy specimens were examined by light and electron microscopy and immunohistology (S-100, HMB45, MART1, CD68, MAC387). Serum/plasma levels of melanocyte growth factors of the patient were determined by enzyme-linked immunosorbent assays and compared with those of normal volunteers (n = 10) and amelanotic patients with metastatic melanoma (n = 10), matched to the UICC stage of the affected patient. Hyperpigmented but otherwise apparently normal skin of the patient displayed epidermal melanocyte hyperplasia, increased melanogenesis, and dermal pigment stored in histiocytes and other cells along with extracellular deposits. Blood levels of alpha-melanocyte stimulating hormone, hepatocyte growth factor, and endothelin-1 were significantly elevated in the affected patient. Aberrant production of these factors may not only be responsible for activation of the pigment system in diffuse melanosis of metastatic melanoma, but also for increased proliferation, motility, and pigment incontinence of normal and malignant melanocytes.

Topics: Adult; alpha-MSH; Case-Control Studies; Endothelin-1; Enzyme-Linked Immunosorbent Assay; Fatal Outcome; Female; Growth Substances; Hepatocyte Growth Factor; Humans; Immunohistochemistry; Melanoma; Melanosis; Skin Neoplasms

To study the pathogenesis of acquired dermal melanocytosis (ADM), we reviewed the clinical, immunohistochemical, and ultrastructural features of 34 cases (female, 33, and male, 1) of ADM. The patients' ages at onset ranged from 8 to 51 years and averaged 26.8 +/- 12.7 years. There was a positive family history. Gray-brown macules were mostly recognized on the face. Not only active dermal melanocytes but also non-pigmented c-KIT- and TRP-2-positive immature melanocytes were detected in the dermis. Taken together those clinical and histological findings, activation of pre-existing immature melanocytes by sunlight, estrogen, and/or progesterone, and some other factors, may be the most likely mode of the development of ADM. Moreover, using cultured murine neural crest cells as a model of c-KIT-positive immature melanocytes, we confirmed that endothelin-1, which is produced and secreted by keratinocytes after UV-irradiation, affects melanocytes and accelerated melanogenesis.

Topics: Adult; Age of Onset; Animals; Biomarkers; Cells, Cultured; Child; Dihydroxyphenylalanine; Endothelin-1; Female; Gonadal Steroid Hormones; Humans; Infant; Intramolecular Oxidoreductases; Japan; Male; Melanocytes; Melanosis; Mice; Middle Aged; Neural Crest; Proto-Oncogene Proteins c-kit; Skin; Sunlight