State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
Department of Disease Proteomics, Chongqing Key Laboratory for Disease Proteomics, Chongqing, China.
Front Immunol. 2022 Jan 28;13:821932. doi: 10.3389/fimmu.2022.821932. eCollection 2022.
As a potential clinical therapeutic cell for injured tissue repair, mesenchymal stem cells (MSCs) have attracted increasing attention. Enhancing the pro-healing function of MSCs has gradually become an essential topic in improving the clinical efficacy of MSCs. Recently, studies have shown that neuronal protein 3.1 (P311) plays a crucial role in promoting skin wound healing, suggesting P311 gene modification may improve the pro-healing function of MSCs. In this study, we demonstrated that increasing the expression of P311 could significantly enhance the ability of MSCs to lessen the number of inflammatory cells, increase the expression of IL10, reduce the levels of TNF-α and IFN-γ, increase collagen deposition, promote angiogenesis, and ultimately accelerate skin wound closure and improve the quality of wound healing. Importantly, we uncovered that P311 enhanced the pro-angiogenesis function of MSCs by increasing the production of vascular endothelial growth factor (VEGF) and . Mechanistically, we revealed that the mTOR signalling pathway was closely related to the regulation of P311 on VEGF production in MSCs. Together, our data displayed that P311 gene modification in MSCs augments their capabilities to promote skin wound closure, which might bring the dawn for its clinical application in the future.
作为一种有潜力的组织损伤修复的临床治疗细胞,间充质干细胞(MSCs)受到了越来越多的关注。增强 MSCs 的促愈功能逐渐成为提高 MSCs 临床疗效的重要课题。最近的研究表明,神经元蛋白 3.1(P311)在促进皮肤伤口愈合中起着关键作用,提示 P311 基因修饰可能改善 MSCs 的促愈功能。在本研究中,我们证明了增加 P311 的表达可以显著增强 MSCs 减轻炎症细胞数量的能力,增加 IL10 的表达,降低 TNF-α 和 IFN-γ 的水平,增加胶原沉积,促进血管生成,最终加速皮肤伤口闭合,改善伤口愈合质量。重要的是,我们发现 P311 通过增加血管内皮生长因子(VEGF)和 的产生来增强 MSCs 的促血管生成功能。在机制上,我们揭示了 mTOR 信号通路与 P311 调节 MSCs 中 VEGF 产生密切相关。总之,我们的数据表明,MSCs 中的 P311 基因修饰增强了它们促进皮肤伤口闭合的能力,这可能为其未来的临床应用带来曙光。