Aims. Forkhead box C1 (FoxC1) is essential for maintaining the hair follicle stem cell niche. The role of FoxC1 in maintaining mesenchymal stem cell (MSC) niches after myocardial infarction (MI) has not been directly determined to date. In this study, we determined to explore the possible roles and mechanisms of FoxC1 on MSC survival and function in the ischemic niche. Methods and Results. MI model was established in this study, and expression level of FoxC1 was overexpressed or knocked down through efficient delivery of FoxC1 transfection or siFoxC1. Fifteen days later, the animals were allocated randomly to receive phosphate-buffered saline (PBS) injection or MSC transplantation. We identified FoxC1 as a key regulator of maintaining the vascular niche in the infarcted hearts (IHs) by driving proangiogenic and anti-inflammatory cytokines while repressing inflammatory and fibrotic factor expression. This vascular niche improved MSC survival and capacity in the IHs. Importantly, FoxC1 interacted with MSCs and was required for vessel specification and differentiation of engrafted MSCs in the ischemic niches, promoting myocardial repair. Inhibiting FoxC1 abolished these effects. Conclusion. These results definitively implicate FoxC1 signaling in maintaining ischemic vascular niche, which may be helpful in myocardial repair induced by MSC therapy.

中文翻译：

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FoxC1 诱导的血管生态位改善梗塞心脏间充质干细胞的存活和心肌修复。

目标。Forkhead box C1 (FoxC1) 对于维持毛囊干细胞生态位至关重要。FoxC1 在心肌梗死 (MI) 后维持间充质干细胞 (MSC) 生态位中的作用尚未直接确定。在这项研究中，我们决心探索 FoxC1 在缺血性生态位中对 MSC 存活和功能的可能作用和机制。方法和结果。本研究建立了 MI 模型，通过 FoxC1 转染或si的有效传递，使 FoxC1 的表达水平过表达或敲低。福克斯C1。十五天后，动物被随机分配接受磷酸盐缓冲盐水（PBS）注射或MSC移植。我们将 FoxC1 鉴定为通过驱动促血管生成和抗炎细胞因子同时抑制炎症和纤维化因子表达来维持梗塞心脏 (IH) 血管生态位的关键调节因子。这种血管生态位提高了 IH 中 MSC 的存活率和容量。重要的是，FoxC1 与 MSCs 相互作用，并且是血管规范和缺血性龛中移植的 MSCs 分化所必需的，促进心肌修复。抑制 FoxC1 消除了这些影响。结论。这些结果明确表明 FoxC1 信号传导在维持缺血性血管生态位中可能有助于 MSC 治疗诱导的心肌修复。