College of Life Science, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, Zhejiang, 310053, People's Republic of China.
Stem Cell Rev Rep. 2020 Aug;16(4):702-710. doi: 10.1007/s12015-019-09947-7.
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.
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。