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Introduction
Vitiligo is a chronic, acquired pigment skin disorder, clinically characterized by well-defined asymptomatic white macules resulting from a loss of functional melanocytes in the epidermis (1). The majority of previous studies on vitiligo have focused on melanocyte abnormalities, but the epidermis structural unit consists of melanocytes with neighboring keratinocytes, and direct cell-to-cell contact and growth factors produced by adjacent keratinocytes regulate the differentiation, proliferation and cell viability of melanocytes (2). Keratinocytes secrete numerous factors that are essential to the survival of melanocytes, which include basic fibroblast growth factor, endothelins, stem cell factor (SCF), hepatocyte growth factor, granulocyte-macrophage colony-stimulating factor, α-melanocyte-stimulating hormone and adrenocorticotropic hormone (3). Previous studies have demonstrated that co-culture of normal human melanocytes with human keratinocytes leads to an increased number of melanocytes (3,4). Therefore, keratinocytes serve an important role in the homeostasis of the epidermis and survival of melanocytes.
Previous studies have revealed that the keratinocytes in depigmented regions of the epidermis in patients with vitiligo exhibited ultrastructural and functional alterations of their mitochondria (5) and had high apoptotic rates (6). In addition, significantly lower expression of SCF has been reported in apoptotic keratinocytes induced by ultraviolet radiation or H2O2 treatment (6). Keratinocyte apoptosis may lead to a loss of survival stimuli and passive melanocyte death. Therefore, it is important to investigate the specific mechanisms of keratinocyte apoptosis in patients with vitiligo and to identify methods to improve the biological activity of keratinocytes in order to alter the local microenvironment of depigmented lesions and enhance the vitality of the local melanocytes.
Among the proteins involved in the cellular biological activity of mammalian cells, including keratinocytes, the small ubiquitin-like modifier (SUMO) is a conserved member of the ubiquitin-related protein family and activates various cellular events, including protein trafficking, cell cycle and chromosome structure and segregation, by conjugating to numerous protein substrates (7–9). SUMOylation and deSUMOylation are dynamic processes. SUMOylation is controlled by an E1-activating enzyme [SUMO-activating enzyme subunit (SAE)1/2], an E2 conjugase [ubiquitin-conjugating enzyme E2 I (Ubc9)] and, in certain cases, the E3 ligases, while deSUMOylation is mediated by SUMO-specific peptidases (SENPs) (10). Previous studies have indicated that the SUMO pathway may be essential for cancer cell survival and tumor progression (11–13). Therefore, SUMOylation may be an important regulator...