The mechanism of epidermal hyperpigmentation in cafe-au-lait macules of neurofibromatosis type 1 (von Recklinghausen's disease) may be associated with dermal fibroblast-derived stem cell factor and hepatocyte growth factor

Abstract

These findings suggest that increased secretion of HGF and SCF by dermal fibroblasts may be associated with the accentuated epidermal melanization observed in CALMs in the skin of NF1 patients.

Hiding in Plain Sight: A Consideration of NF1-Associated Hypovitaminosis D and its Treatment

“…Consistent with the documentation of high mast cell density in one type of NF1 lesion-neurofibromas-Okazaki et al [26] documented increased mast cell densities in NF1 CLS (140/mm2) and non-CLS NF1 skin (50/mm2) compared to non-NF1 non-CLS (control) skin (15/mm2). Three years later, in 2006, De Schepper et al27 examined the mast cell density in four types of specimens: NF1 CLS, NF1 "normal" skin, control subject CLS and control subject "normal" skin.…”

The Treatment of Solar Lentigo using Dr. Hoon Hur's Optimal Melanocytic Suicide-2 Parameter with a High fluence 1064nm Nd:YAG Laser without Postinflammatory Hyperpigmentation

“…The pulse stacking technique for 3 seconds to the solar lentigo is very important to destroy the epidermal melanocytes with minimizing the epidermal damage. If the pulse stacking technique for more than 3 seconds to the solar lentigo was performed, the epidermal damages might have occurred and the damaged keratinocytes might have secreted the keratinocytic injury-induced cytokines such as endothelin-1, α-MSH, ACTH, bFGF, and prostaglandin (PGE2, PGF2α) which activate melanocytes and increase melanin synthesis in the melanosomes, therefore causing PIH and worsening solar lentigo [7][8][9][10][11]. In case of solar lentigo on face, 8 sessions of OMS-2 Parameter Therapy are performed once a week.…”

“…Then, the fibroblasts mainly secrete Stem Cell Factor (SCF) and Hepatocyte Growth Factor (HGF) which activate melanocytes and increase melanin synthesis in the melanosomes, eventually causing PIH and worsening solar lentigo [7][8][9][10][11]. Finally, reactive oxygen species such as nitric oxide, free radical oxygen and peroxide, generated from the damaged keratinocytes also activate melanocytes and increase melanin synthesis in the melanosomes, eventually causing PIH and worsening solar lentigo [7][8][9][10][11]. To avoid the side effects such as PIH, scarring and worsening solar lentigo of the conventional laser therapy, the authors devised Dr. Hoon Hur's optimal melanocytic suicide-2(OMS-2) parameter therapy with a high fluence 1064nm Q-switched Nd:YAG laser without side effects or recurrences.…”

“…IL-1 stimulates keratinocytes to secrete endothelin-1, α-Melanocyte Stimulating Hormone (MSH), Adrenocorticotropic Hormone (ACTH) and Prostaglandin(PGE2,PGF2α). These keratinocytic injury-induced cytokines activate melanocytes and increase melanin synthesis in the melanosomes, therefore causing PIH and worsening solar lentigo [7][8][9][10][11]. The damged keratinocytes also secrete the single-chain urokinase type plasminogen activator (sc-uPA).…”

“…The sc-uPA converts plasminogen to plasmin, which stimulates the keratinocytes to secrete basic fibroblast growth factor (bFGF). Again bFGF activates the melanocytes and increases melanin synthesis in the melanosomes, therefore causing PIH and worsening solar lentigo [7][8][9][10][11].…”