Lipocalin‐type prostaglandin D synthase as a marker for the proliferative potential of melanocyte‐lineage cells in the human skin

Abstract

Melanocytes in the human epidermis actively produce and secrete various substances, thereby contributing to the maintenance of the skin homeostasis. Lipocalin-type prostaglandin D synthase (L-PGDS) that catalyzes the formation of prostaglandin D(2) (PGD(2) ) may be one of such secreted molecules. Once secreted, L-PGDS functions as a transporter for lipophilic ligands, including all-trans retinoic acid (RA). L-PGDS, therefore, may possess pleiotropic functions in the skin through PGD(2) and RA. We aimed to identify the cell types that express L-PGDS in human skin and to explore the role of L-PGDS in the growth potential of melanocyte-lineage cells. Immunohistochemical analysis for L-PGDS expression was performed with the tissue sections that were prepared from five malignant melanomas, six nevus cell nevi and one Spitz nevus. Normal skin tissues adjacent to the excised melanoma tissues were also analyzed. L-PGDS is expressed in epidermal melanocytes but its expression is undetectable in keratinocytes. Moreover, L-PGDS is undetectable in most benign nevus cells, which may reflect the marginally accelerated proliferation of nevus cells. In contrast, L-PGDS is overexpressed in malignant melanomas, although the frequency of L-PGDS-positive cells was variable (15-50%), depending on the specimens. Lastly, RNA interference analysis against human L-PGDS was performed with short interfering RNA. Knockdown of L-PGDS expression with short interfering RNA in cultured cells suggests that L-PGDS may restrict cell proliferation through RA. In conclusion, L-PGDS expression may contribute to the restricted proliferation of epidermal melanocytes, but conversely its overexpression may reflect the dysregulated proliferation of melanoma cells.

In situquantification of individual mRNA transcripts in melanocytes discloses gene regulation of relevance to speciation

“…The observation of the present study that HPGDS transcripts were limited to melanocytes lends further support to a potential role in melanogenesis. Moreover, just as MITF, it was expressed at an early stage of melanocyte maturation which is consistent with the proposition that it may be involved in regulatory feed-back with MITF (Shimanuki et al, 2012; Takeda et al, 2006). Additionally, in human cell lines, it had been shown that prostaglandins positively enhanced tyrosinase activity (Abdel-Malek et al, 1987).…”

The prostaglandin synthases, COX-2 and L-PGDS, mediate prostate hyperplasia induced by low-dose bisphenol A

“…In vitro studies have indicated that L-PGDS mediates cell proliferation via its lipid-carrying function in different cells. In human epidermal melanocytes, normal L-PGDS levels restrict the growth of epidermal melanocytes by transporting all-trans retinoic acid (RA), while its overexpression dysregulates the proliferation of melanoma cells 56 . Additionally, the protein L-PGDS accelerates the migration of glial cells and promotes reactive gliosis by interacting with protein kinase C substrate (MARCKS) 57 .…”

β-Trace Protein: A Marker of GFR and Other Biological Pathways

“…18 PGD 2 is involved in a wide range of physiologic functions such as sleep induction and regulation, nociception, bronchoconstriction, adipocyte differentiation, nitric oxide release and induction of vasodilation, inflammatory mediator modulation, and inhibition of platelet aggregation. 36 Recent studies also suggest a role for BTP/PGD 2 in maintenance of skin homeostasis, 21 bone remodeling, 24 hair growth inhibition, 22 and immune system modulation in inflammatory conditions of the gastrointestinal tract. 23,37 PGD 2 is metabolized further to other prostanoids such as J series prostaglandins, identified to date only in vitro and therefore with a controversial biological role, and 9a11b-PGF 2 , a mediator of bronchoconstriction.…”

“…18 In the heart, BTP has been localized to myocardial cells, atrial endocardial cells, synthetic state intimal smooth muscle cells, and fibrous plaques of atherosclerotic stenosed coronary arteries (but not within normal coronary arteries). 18,19 BTP has been described in vascular endothelial cells, 20 skin melanocytes and keratinocytes, 21,22 gastric mucosal epithelial cells, 23 bone osteoblasts, 24 and adipocytes. 25 Within the monkey kidney, BTP localizes to cells of the proximal tubules, loop of Henle, and glomerulus.…”