BACKGROUND Vitiligo is an acquired chronic and recurrent skin disease that causes a depigmentation disorder, resulting in selective destruction of melanocytes (MC). However, the mechanism that leads to melanocyte dysfunction and death remains unclear. METHODS We performed RNA sequencing, immunohistochemistry, and immunoblotting to characterize the patterns of phosphatase and tensin homolog (PTEN)/phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) pathway activation in vitiligo. We also cocultured primary melanocytes with mesenchymal stem cells (MSCs) in a Transwell system to explore how MSCs inhibit the PTEN/PI3K/AKT pathway in melanocytes. RESULTS We identified that vitiligo normal-lesional junction skin presented with high expression of PTEN, which led to the inhibition of AKT phosphorylation (p-AKT) at S-473. Furthermore, PTEN overexpression led to oxidative stress-induced apoptosis in melanocytes. Coculturing with MSCs enhanced the cell proliferation of human melanocytes and repressed PTEN expression, which inhibited oxidative stress-induced apoptosis. CONCLUSION We report that vitiligo patients present with high PTEN expression, which may play a role in the impairment of melanocytes. Furthermore, our study provides evidence that MSCs target the PTEN/PI3K/AKT pathway to regulate cell proliferation and apoptosis in human melanocytes, indicating that MSCs may serve as a promising therapy for vitiligo.

中文翻译：

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间充质干细胞通过白癜风中的PTEN途径促进人黑素细胞的增殖和对细胞凋亡的抗性。

背景技术白癜风是一种引起色素沉着紊乱，导致黑素细胞（MC）的选择性破坏的获得性慢性和复发性皮肤病。但是，导致黑素细胞功能障碍和死亡的机制仍不清楚。方法我们进行了RNA测序，免疫组化和免疫印迹分析，以表征白癜风中磷酸酶和张力蛋白同源物（PTEN）/磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（AKT）通路的模式。我们还在Transwell系统中将原代黑素细胞与间充质干细胞（MSC）共培养，以探索MSC如何抑制黑素细胞中的PTEN / PI3K / AKT途径。结果我们确定白癜风正常病变交界处的皮肤呈现PTEN的高表达，从而导致S-473的AKT磷酸化（p-AKT）受到抑制。此外，PTEN过度表达导致氧化应激诱导的黑素细胞凋亡。与MSC共培养可增强人黑素细胞的细胞增殖并抑制PTEN表达，从而抑制氧化应激诱导的细胞凋亡。结论我们报告白癜风患者表现出高PTEN表达，这可能在黑素细胞受损中起作用。此外，我们的研究提供了证据表明MSC靶向PTEN / PI3K / AKT通路来调节人黑素细胞的细胞增殖和凋亡，这表明MSC可以作为白癜风的有前途的疗法。结论我们报告白癜风患者表现出高PTEN表达，这可能在黑素细胞受损中起作用。此外，我们的研究提供了证据表明MSC靶向PTEN / PI3K / AKT通路来调节人黑素细胞的细胞增殖和凋亡，这表明MSC可以作为白癜风的有前途的疗法。结论我们报告白癜风患者表现出高PTEN表达，这可能在黑素细胞受损中起作用。此外，我们的研究提供了证据表明MSC靶向PTEN / PI3K / AKT通路来调节人黑素细胞的细胞增殖和凋亡，这表明MSC可以作为白癜风的有前途的疗法。