Biology subjects

Sayo, T.

Publications and source records attributed to Sayo, T..

3 recordsLinked to original sources

bioRxiv2025

The fate of melanocytes and the disorganization of basement membrane in a guinea pig model of Rhododendrol-induced chemical vitiligo

BackgroundRhododendrol (RD) is a phenolic compound that was first developed as a skin-lightening agent that occasionally induces skin depigmentation. Although it has been shown that RD induces melanocyte death in vitro, it is still not fully understood why melanocytes are gone by RD in vivo. ObjectiveThis research aimed to investigate how melanocytes are eliminated in the animal model by RD. MethodsOn the backs of black guinea pigs (JY-4) with epidermal melanocytes in the basal layer, 30% RD was administered topically three times per day, five days per week. Skin tissues were collected sequentially and histologically analyzed. ResultsOn day 21, L* values in the RD-applied skin were significantly higher than in the vehicle-applied skin. From day 1 to day 7, the number of TRP1-positive melanocytes and melanin in the basal layer decreased, but no TUNEL-positive melanocytes were identified. On the other hand, an accumulation of melanin was newly found in the dermis. Immunohistochemical staining identified several melanocytes in the upper dermis or spinous layer, away from the basement membrane. An investigation of the epidermal-dermal interface showed a structural anomaly in a portion of the basement membrane with elevated MMP2 expression and increased dermal fibroblasts. The application of the MMP2 inhibitor Ilomastat abolished the basement membrane abnormality by RD. ConclusionThese findings suggest that RD-induced alterations in basement membrane structure may contribute to melanocyte detachment and loss, which is the cause of skin depigmentation not only in RD-induced vitiligo but also in vitiligo.

pathology↗

bioRxiv2025

Altered laminin signaling destinates melanocyte reprogramming in vitiligo

Vitiligo is an acquired depigmenting skin disorder characterized by progressive melanocyte loss, but the cellular mechanisms driving this process remain unclear. Here, we identify melanocyte dedifferentiation as a central and reversible pathogenic mechanism in vitiligo. In healthy human skin, melanocytes reside within a basement membrane niche defined by dystroglycan-laminin-211 adhesion. In contrast, vitiligo lesions exhibit aberrant extracellular matrix remodeling, leading to an adhesion switch to integrin 3{beta}1-laminin-332 interactions. This shift promotes melanocyte dedifferentiation via Rho-F-actin-dependent activation of Hippo and MAPK pathways, resulting in c-Jun-mediated transcriptional changes. Dedifferentiated melanocytes lose their pigment-producing identity and acquire neural crest-like features with multilineage potential. Importantly, this process is reversible. Pharmacological inhibition of involved pathways restores melanocyte differentiation and induces repigmentation in both vitiligo mouse models and ex vivo patient skin. Notably, JAK inhibitors also promote redifferentiation independently of immune modulation. These findings uncover melanocyte dedifferentiation as a fundamental driver of vitiligo and a tractable therapeutic target, offering new opportunities for therapeutic intervention.

cell biology↗

bioRxiv2022

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

Vitiligo, a chronic autoimmune skin disorder characterized by selective epidermal melanocyte loss, lacks a well-defined mechanism for this phenomenon. Our study offers compelling insights into vitiligo pathogenesis by revealing disruptions in the basement membrane zone (BMZ) architecture. We observed branched, fragmented, and multilayered lamina densa, accompanied by elevated dermal fibroblast numbers and notable matrix metalloproteinase 2 (MMP2) overexpression. Vitiliginous skin extracts exhibited significant active MMP2 upregulation. To establish a direct link, we intradermally injected MMP2-overexpressing fibroblasts into K14-SCF transgenic mice, resulting in vitiligo-like skin and melanocyte loss, effectively reversed by coadministering MMP2 inhibitors. These groundbreaking findings highlight the pivotal role of disorganized BMZ in vitiligo, proposing MMP2 overexpression in dermal fibroblasts as a potential key contributor. Enhancing our understanding of vitiligos mechanisms, this research opens avenues for innovative therapeutic strategies against this challenging autoimmune skin disorder. TeaserDisrupted skin architecture and MMP2 in dermal fibroblasts hold the key to a potential breakthrough against this puzzling autoimmune disease vitiligo.

pathology↗