PMID- 24223113
OWN - NLM
STAT- MEDLINE
DCOM- 20140820
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 11
DP  - 2013
TI  - HGF/SF increases number of skin melanocytes but does not alter quality or 
      quantity of follicular melanogenesis.
PG  - e74883
LID - 10.1371/journal.pone.0074883 [doi]
LID - e74883
AB  - Melanins 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.
FAU - Wolnicka-Glubisz, Agnieszka
AU  - Wolnicka-Glubisz A
AD  - Department of Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, 
      Jagiellonian University, Krakow, Poland.
FAU - Pecio, Anna
AU  - Pecio A
FAU - Podkowa, Dagmara
AU  - Podkowa D
FAU - Plonka, Przemyslaw Mieszko
AU  - Plonka PM
FAU - Grabacka, Maja
AU  - Grabacka M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131106
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (HGF protein, mouse)
RN  - 0 (Melanins)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 1.14.18.1 (Monophenol Monooxygenase)
SB  - IM
MH  - Animals
MH  - Hair/metabolism
MH  - Hair Follicle/*cytology
MH  - Hepatocyte Growth Factor/*physiology
MH  - Melanins/*biosynthesis
MH  - Melanocytes/*physiology/ultrastructure
MH  - Melanosomes/metabolism/ultrastructure
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Monophenol Monooxygenase/metabolism
MH  - Skin Pigmentation
PMC - PMC3819350
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/11/14 06:00
MHDA- 2014/08/21 06:00
PMCR- 2013/11/06
CRDT- 2013/11/14 06:00
PHST- 2013/06/21 00:00 [received]
PHST- 2013/08/06 00:00 [accepted]
PHST- 2013/11/14 06:00 [entrez]
PHST- 2013/11/14 06:00 [pubmed]
PHST- 2014/08/21 06:00 [medline]
PHST- 2013/11/06 00:00 [pmc-release]
AID - PONE-D-13-25802 [pii]
AID - 10.1371/journal.pone.0074883 [doi]
PST - epublish
SO  - PLoS One. 2013 Nov 6;8(11):e74883. doi: 10.1371/journal.pone.0074883. eCollection 
      2013.