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二甲草酰甘氨酸调控间充质干细胞中的 HIF-1 信号通路。

Dimethyloxalyl Glycine Regulates the HIF-1 Signaling Pathway in Mesenchymal Stem Cells.

机构信息

College of Life Science, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, Zhejiang, 310053, People's Republic of China.

出版信息

Stem Cell Rev Rep. 2020 Aug;16(4):702-710. doi: 10.1007/s12015-019-09947-7.

Abstract

Mesenchymal stem cells (MSCs) are pluripotent stem cells with self-renewal and multidirectional differentiation capabilities. Dimethyloxalyl glycine (DMOG) mobilizes MSCs, and the hypoxia inducible factor-1 (HIF-1) signaling pathway plays an important role in MSC mobilization. We aimed to investigate the effect of DMOG on the HIF-1 pathway in MSCs. Rats were treated with DMOG, and the numbers of peripheral blood MSCs (PB-MSCs) and bone marrow MSCs (BM-MSCs) were detected by the Colony-forming unit fibroblastic (CFU-F) method. The growth curve, cell cycle and migration ability of PB-MSCs and BM-MSCs were detected by CCK-8, Flow cytometry and Transwell assays. Western blotting and real-time qPCR were used to detect the expression of the HIF-1 pathway. The number of bone marrow microvessels was detected by immunohistochemistry. DMOG significantly increased the numbers of PB-MSCs and BM-MSCs (P < 0.05). Further, the MSCs in peripheral blood and bone marrow still had the ability to proliferate and migrate after mobilization by DMOG. The expression levels of HIF-1α, stromal cell-derived factor-1α (SDF-1α) and vascular endothelial growth factor (VEGF) in MSCs were significantly regulated by DMOG (P < 0.05). The number of bone marrow microvessels decreased after the VEGF/VEGFR signaling pathway was blocked by SU5416 (P < 0.05). Therefore, these findings demonstrated that DMOG regulates the HIF-1α signaling pathway and promotes biological effects in MSCs.

摘要

间质干细胞(MSCs)是具有自我更新和多向分化能力的多能干细胞。二甲基草酰甘氨酸(DMOG)动员 MSCs,而缺氧诱导因子-1(HIF-1)信号通路在 MSC 动员中发挥重要作用。我们旨在研究 DMOG 对 MSCs 中 HIF-1 通路的影响。用 DMOG 处理大鼠,通过集落形成单位成纤维细胞(CFU-F)法检测外周血 MSCs(PB-MSCs)和骨髓 MSCs(BM-MSCs)的数量。通过 CCK-8、流式细胞术和 Transwell 检测 PB-MSCs 和 BM-MSCs 的生长曲线、细胞周期和迁移能力。Western blot 和实时 qPCR 用于检测 HIF-1 通路的表达。免疫组织化学用于检测骨髓微血管的数量。DMOG 显著增加了 PB-MSCs 和 BM-MSCs 的数量(P<0.05)。此外,DMOG 动员后外周血和骨髓中的 MSC 仍具有增殖和迁移的能力。DMOG 显著调节 MSC 中 HIF-1α、基质细胞衍生因子-1α(SDF-1α)和血管内皮生长因子(VEGF)的表达水平(P<0.05)。在用 SU5416 阻断 VEGF/VEGFR 信号通路后,骨髓微血管的数量减少(P<0.05)。因此,这些发现表明 DMOG 调节 HIF-1α 信号通路并促进 MSCs 的生物学效应。

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