Abstract：
The basement membrane zone is the interface between the epidermis and dermis, and it is disrupted in several skin conditions. Here, we report the results of a comprehensive investigation into the structural and molecular factors of the basement membrane zone in vitiligo, a dermatological disorder characterised by depigmented patches on the skin. Using electron microscopy and immunofluorescence staining, we confirmed abnormal basement membrane zone morphology and disrupted basement membrane zone architecture in human vitiliginous skin. Furthermore, we identified elevated expression of matrix metalloproteinase 2 (MMP2) in human dermal fibroblasts as a key factor responsible for basement membrane zone matrix degradation. In our in vitro and ex vivo models, overexpression of MMP2 in fibroblasts led to basement membrane zone disruption and melanocyte disappearance. Importantly, we reveal that the loss of melanocytes in vitiligo is primarily linked to their weakened adhesion to the basement membrane, mediated by binding between integrin β1 and laminin and discoidin domain receptor 1 and collagen IV. Finally, inhibition of matrix metalloproteinase 2 expression reversed depigmentation in a mouse model of vitiligo. In conclusion, our research shows the importance of basement membrane zone integrity in melanocyte residence and offers new avenues for therapeutic interventions to address this challenging skin condition. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
摘要：
基底膜区是表皮和真皮之间的界面，它在几种皮肤状况下被破坏。这里,我们报告了对白癜风基底膜区的结构和分子因素进行全面调查的结果，一种皮肤病，其特征是皮肤上的色素斑。使用电子显微镜和免疫荧光染色，我们证实了人类白癜风皮肤的基底膜区形态异常和基底膜区结构破坏。此外，我们确定人真皮成纤维细胞中基质金属蛋白酶2（MMP2）的表达升高是导致基底膜区基质降解的关键因素。在我们的体外和离体模型中，MMP2在成纤维细胞中的过表达导致基底膜区破坏和黑素细胞消失。重要的是,我们发现白癜风黑素细胞的丢失主要与它们对基底膜的粘附减弱有关，通过整合素β1与层粘连蛋白和盘状结构域受体1和胶原IV之间的结合介导。最后,白癜风小鼠模型中基质金属蛋白酶2表达的抑制逆转了色素脱失。总之,我们的研究显示了基底膜区完整性在黑素细胞驻留中的重要性,并为治疗性干预提供了新的途径,以解决这一具有挑战性的皮肤状况.©2024作者（S）。由JohnWiley＆SonsLtd代表英国和爱尔兰病理学会出版的病理学杂志。
