Fibroblast morphology, growth rate and gene expression in facial melasma

ABSTRACT

Abstract Background: In addition to melanocytic hyperfunction, changes are observed in the upper dermis of melasma, and fibroblasts play a central role in collagen synthesis and pigmentation induction. Objective: To explore the morphology, growth rate, and gene expression profile of fibroblasts from the skin with melasma in comparison to fibroblasts from the adjacent healthy skin. Methods: Ten women with facial melasma were biopsied (lesion and adjacent healthy skin), and the fragments were processed for fibroblast culture. Samples from five participants were seeded to evaluate growth (days 2, 5 and 8) and senescence (SA-β-gal) curves. The samples from the other participants were submitted to real-time PCR to comparatively evaluation of the expression of 39 genes. Results: Cultured fibroblasts from melasma skin were morphologically less fusiform in appearance and on average a 34% (95% CI 4%-63%) greater proportion of cells labeled with SA-β-gal than the fibroblasts from the adjacent skin. The cell growth rate was lower for the melasma samples after eight days (p < 0.01). The WNT3A, EDN3, ESR2, PTG2, MMP1, and SOD2 genes were up-regulated, whereas the COL4A1, CSF2, DKK3, COL7A1, TIMP4, CCL2, and CDH11 genes were down-regulated in melasma skin fibroblasts when compared to the ones from adjacent healthy skin. Study limitations: Small sample size; absence of functional tests. Conclusions: Fibroblasts from the skin with melasma showed a lower growth rate, less fusiform morphology and greater accumulation of SA-β-gal than those from adjacent photo exposed skin. Moreover, their gene expression profile comprised factors that may contribute to upper dermis damage and sustained melanogenesis.