HMGB3/Wnt/β-Catenin信号轴影响UVB治疗白癜风效果的机制研究

白癜风是严重影响患者身心健康的慢性皮肤病，UVB光疗是重要的治疗手段，UVB不仅可促进黑素细胞（MC）再生，还能促进其黏附于角质形成细胞（KC），但具体机制不清。我们单细胞测序结果显示白癜风皮损处HMGB家族蛋白高表达的KC亚群显著增多。以往研究表明HMGB3可通过Wnt/β-Catenin信号传导调控干细胞生物功能，提示该通路激活能促进MC再生。进一步我们发现，UVB可促进KC表达HMGB3，进而促进E-钙粘蛋白/β-Catenin复合体的活化释放和细胞骨架的改变。由此我们推测，UVB可通过激活HMGB3/Wnt/β-Catenin信号轴促进MC再生及其与KC间黏附互作，促进表皮复色。本课题旨在明确UVB通过HMGB3/Wnt/β-Catenin轴调控细胞骨架和黏附功能的具体机制，利用皮肤三维模型证实其对MC生物学活性的影响，探究UVB治疗白癜风的作用机制，为提高疗效提供新的思路和方向。

Vitiligo is a chronic skin disease that seriously affects the physical and mental health of patients. UVB phototherapy is an important treatment method. UVB can not only promote the regeneration of melanocytes, but also its adhesion to keratinocytes, while the specific mechanism is still unclear. Our single-cell transcriptome atlas results showed a significant increase in KC subpopulations with high expression of HMGB family proteins in vitiligo lesions. Previous studies have shown that HMGB3 can regulate stem cell biological functions through Wnt / β-Catenin signaling, suggesting that activation of this pathway can promote MC regeneration. Furthermore, we found that UVB can promote the expression of HMGB3 in KC, and then promote the activation and release of E-cadherin / β-Catenin complex and the change of cytoskeleton. From this we speculate that UVB can promote MC regeneration and its interaction with KC by activating the HMGB3 / Wnt / β-Catenin signal axis,then recovery the complexion of the epidermis. We will use a three-dimensional skin model to confirm its effect on MC biological activity and to clarify the specific mechanism of UVB regulating the cytoskeleton and adhesion function through the HMGB3 / Wnt / β-Catenin axis.The purpose of this project is to investigate the mechanism of UVB in the treatment of vitiligo to improve the efficacy . It will open up new research ideas and treatments.