Disorganization of basement membrane zone architecture causes impaired melanocyte inhabitation in vitiligo

Vitiligo is a common but puzzling skin disorder characterized by the selective loss of epidermal melanocytes due to unknown mechanisms. Here, we show patients with vitiligo have disruptions of basement membrane zone (BMZ) architecture including branched, fragmented, and multilayered lamina densa with increased numbers of dermal fibroblasts and overexpression of MMP2 in those cells. Extracts of vitiliginous skin showed increased MMP2 protein expression, with a large portion of the MMP2 proteins in the active form. Intradermal injection of MMP2-overexpressing fibroblasts in K14-SCF transgenic mice induced a vitiligo-like skin appearance and disappearance of melanocytes, which were reversed by coadministration of MMP2 inhibitors. These results suggest that disorganization of the BMZ driven by MMP2 overexpression in dermal fibroblasts may cause the impaired melanocyte inhabitation observed in vitiligo.