Pigmentation: The Role of Blood Vessels

-Skin pigmentation is due to incresed melanin content in melanocytes.
-In lesions such as melasma (chloasma, pregnancy mask), there is an increased density of blood vessels and those are suggested to play a role.

Endothelin 1 (ET-1) is secreted from blood vessels and has been shown to act in various pigmentary conditions as well as in lesions close to age spots (seborrheic keratosis*)

Findings
-In the presence of endothelial cells in melasma lesions, the pigmentation of melanocytes and ox ex-vivo cultures human skin is REDUCED.
–UV-irradiation of non-stimulated melanocytes induces pigmentation

Genetic expression profiling of irradiated melanocytes shows that this acts by upregulation of ET-1; indeed the pigmentogenic action is stopped by inhibiting the Et-1 receptor.

This study suggests that:
-the role of blood vessels in inducing pigmentation could be applicable to pigmentation of many skin lesions, not just in isolated conditions such as melasma
-non-stimulated endothelial cells protect against pigmentation. However they induce melanogenesis once irradiated.

*Pigmentation in SK
-The mechanism in classical SK of pigmentation is unknown. It has nevertheless been studied in melanoacanthoma, a histologically close lesion to SK, which is sometimes considered as a subtype of SK, but is located in the mucuous membranes. Pigmentation in SK is postulated to come from the activation of the endothelin receptor by endothelin-1 (ET-1) {Teraki, 1996}. ET-1, whose production is stimulated by UVB light {Kadono, 2001} is produced by endothelin converting enzyme 1 (ECE-1). Identification of ET-1 was done using immunohistochemistry and reverse transcriptase-polymerase chain reaction(RT-PCR) on seven acanthotic and pigmented SKs. RT-PCR revealed an increase in mRNA of ET-1 and tyrosinase, suggesting an ET-1 role in pigmentation. The postulated mechanism of action is as follows :.
-Endothelin then acts on the neighboring melanocytes (paracrine regulation) which express the endothelin receptor and induces melanocyte mitosis and production of melanin {Imokawa, 1992; Yada, 1991}. Then the melanocytes transfer their melanosomes to the neighbouring keratinocytes {Sanderson, 1968}.

Source of information: L-20 Park JY et al. Endothelial cells regulate skin pigmentation. JSID Annual Meeting (Japanese Society of Investigative Dermatology, 日本研究皮膚科学会) 2015 – Okayama, Japan