Role of fibroblast-derived growth factors in regulating hyperpigmentation of solar lentigo.
BACKGROUND
Cutaneous pigmentation is regulated by a complex melanogenic network in which both keratinocytes and fibroblasts synthesize growth factors and cytokines. Solar lentigo (SL) is characterized by hyperpigmented lesions occurring on photodamaged skin areas. Despite the association of SL to ultraviolet (UV) exposure, the mechanisms underlying the development of these spots are not completely defined.


OBJECTIVE
To analyse the involvement of the fibroblast-derived growth factors, hepatocyte growth factor (HGF), keratinocyte growth factor (KGF) and stem cell factor (SCF) in SL hyperpigmentation; to evaluate whether the photoageing process occurring in fibroblasts could be responsible for the altered expression of these cytokines; and to investigate a new possible role of KGF in regulating pigmentation through the specific induction of melanogenic cytokines by keratinocytes.


METHODS
We performed immunohistochemical analysis of HGF, KGF and SCF on SL biopsies. We analysed the mRNA expression of these cytokines using an in vitro model of photoageing induced on fibroblasts. Finally, we evaluated the effects of KGF on the expression of melanogenic cytokines at the mRNA and protein levels on keratinocytes.


RESULTS
We found positive staining for HGF, KGF and SCF in the upper dermis of SL lesions and a significant induction of the three cytokines in photoaged fibroblasts. We also demonstrated the contribution of KGF to pigmentation, showing its ability specifically to modulate the expression of SCF in keratinocytes.


CONCLUSIONS
Fibroblasts may be persistently activated by UV exposure to release melanogenic growth factors; this inducible cytokine network acts both directly and indirectly through keratinocytes and may contribute to the hyperpigmentation of SL.
Kovacs
D
D
San Gallicano Dermatologic Institute, IRCCS, Via Elio Chianesi 53, Rome 00144, Italy.
Cardinali
G
G
Aspite
N
N
Cota
C
C
Luzi
F
F
Bellei
B
B
Briganti
S
S
Amantea
A
A
Torrisi
M R
MR
Picardo
M
M
D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D015153:Blotting, Western; D005260:Female; D051523:Fibroblast Growth Factor 7 / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D017495:Hyperpigmentation / Q000209:etiology / Q000378:metabolism*; D007150:Immunohistochemistry; D007911:Lentigo / Q000209:etiology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010787:Photosensitivity Disorders / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D015595:Skin Aging / Q000502:physiology; D019089:Stem Cell Factor / Q000378:metabolism*; D013472:Sunlight / Q000009:adverse effects*
D012333:RNA, Messenger; D019089:Stem Cell Factor; D051523:Fibroblast Growth Factor 7; D017228:Hepatocyte Growth Factor