HGF/SF Increases Number of Skin Melanocytes but Does Not Alter Quality or Quantity of Follicular Melanogenesis
Agnieszka Wolnicka-Glubisz , Anna Pecio , Dagmara Podkowa , Przemysław Mieszko Płonka , Maja Grabacka
AbstractMelanins are an important factor determining the vulnerability of mammalian skin to UV radiation and thus to UV-induced skin cancers. Transgenic mice overexpressing hepatocyte growth factor/scatter factor (HGF/SF) have extra-follicular dermal melanocytes, notably in the papillary upper dermis, and are susceptible to UV-induced melanoma. Pigmented HGF/SF neonatal mice are more susceptible than albino HGF/SF animals to UVA -induced melanoma, indicating an involvement of melanin in melanoma formation. This raises the question of the effect of transgenic HGF/SF on melanization. We developed a methodology to accurately quantitate both the production of melanin and the efficiency of melanogenesis in normal, and HGF/SF transgenic mice in vivo. Skin and hair shafts of 5 day old and adult (3 week old) C57BL/6-HGF/SF and corresponding C57BL/6 wild type mice were investigated by electron paramagnetic resonance spectroscopy (EPR) to quantitate melanin, by transmission electron microscopy (TEM) for the presence of melanosomes, and by standard histology and by Western blotting and zymography to determine the expression and activity of melanogenesis-related proteins. Eumelanin but no phaeomelanin was detected in transgenic C57BL/6-HGF and C57BL/6 wild type mice. Transgenic HGF/SF overexpression did not change the type of melanin produced in the skin or hair, did not affect the terminal content of melanin production in standard samples of hair and did not influence hair cycle/morphogenesis-related changes in skin thickness. No melanocytes were found in the epidermis and no melanosomes were found in epidermal keratinocytes. HGF/SF transgenic mice thus lack the epidermal melanin UV-protection found in constitutively dark human skin. We conclude that melanocytes in the HGF/SF transgenic mouse, particularly in the papillary dermis, are vulnerable to UVA which interacts with eumelanin but not phaeomelanin to induce melanoma.
|Journal series||Plos One, ISSN 1932-6203, (A 35 pkt)|
|Publication size in sheets||0.5|
|Score|| = 40.0, 26-07-2017, ArticleFromJournal|
= 40.0, 26-07-2017, ArticleFromJournal
|Publication indicators||= 7|
|Citation count*||12 (2016-05-09)|
|Finansowanie||M.G. is supported by the Foundation for Polish Science-POMOST program co-financed by the European Union with in European Regional Development Fund. A.W-G was supported by Faculty BBBt, UJ, BW-2010. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.|
* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.