Oral communication, CS8 / C30

Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011

Fibroblasts regulate both physiological and pathological pigmentation of skin in vitro and in vivo

We have previously described that white human skin or white human epidermal reconstructs xenografted onto nude mice could become black or totally white. The increase in human epidermal pigmentation was shown to be associated with an increase in melanin content and melanosome transfer whereas the white pattern was associated with a disappearance of melanocytes, like in vitiligo. These modifications of pigmentary pattern were associated with changes in densities of dermal fibroblasts. In vitro, we have compared reconstructs made on dead de-epidermized dermis colonized or not with various concentrations of fibroblasts or treated with fresh or frozen media conditioned by various densities of human or murine fibroblasts and we have reproduced this phenomenon of increase or decrease of pigmentation. We have noticed that FGF2, which stimulate melanin secretion, and cytokeratin 5, which is associated with melanosome transfer, were overexpressed in epidermis of hyperpigmented samples. In vitro treatment of reconstructed epidermis without fibroblasts with FGF2 increased cytokeratin 5 expression. Using our model of reconstructed epidermis with fibroblasts of systemic scleroderma (SSc) patients, which in addition to fibrosis have pigmentation changes, we were able to demonstrate that SSc fibroblasts can either stimulate or inhibit pigmentation according to patients. To better understand the dermal influence on pigmentation we compared lesional and perilesional skin of a patient with a pronounced depigmentation following erythema multiforme for TRP-1, MelanA, Vimentin, K5, FGF2, expression. We found that the number of melanocytes was decreased in lesional skin and that the remaining melanocytes were non functional (TRP-1 negative) which may explain the depigmentation. Interestingly, FGF2 was overexpressed in lesional area whereas densities of fibroblasts and K5 expression were similar in both areas. Since all these data point out the key role of FGF2 we are using our model of reconstructs with FGF2 overexpressing fibroblasts to detect changes in pigmentation. In conclusion, our data associated with clinical observations of pigmentary disorders support the hypothesis that fibroblasts modulate pigmentation by paracrine factors especially FGF2.

Advertisement from our sponsor: