Translational Medicine Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan, 450007, China.
Stem Cell Research Center, Henan Key Laboratory of Stem Cell Differentiation and Modification Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, China.
Curr Stem Cell Res Ther. 2023;18(1):93-104. doi: 10.2174/1574888X17666220429103935.
The prevalence of obesity, as well as obesity-induced chronic inflammatory diseases, is increasing worldwide. Chronic inflammation is related to the complex process of angiogenesis, and we found that adipose-derived stem cells from obese subjects (obADSCs) had proangiogenic features, including higher expression levels of interleukin-6 (IL-6), Notch ligands and receptors, and proangiogenic cytokines, than those from control subjects. We hypothesized that IL-6 and Notch signaling pathways are essential for regulating the proangiogenic characteristics of obADSCs.
This study aimed to investigate whether the inflammatory cytokine interleukin 6 (IL-6) promotes the proangiogenic capacity of adipose stem cells in obese subjects via the IL-6 signaling pathway.
We compared the phenotype analysis as well as cell doubling time, proliferation, migration, differentiation, and proangiogenic properties of ADSCs in vitro. Moreover, we used small interfering RNAs to inhibit the gene and protein expression of IL-6.
We found that ADSCs isolated from control individuals (chADSCs) and obADSCs had similar phenotypes and growth characteristics, and chADSCs had a stronger differentiation ability than obADSCs. However, obADSCs were more potent in promoting EA.hy926 cell migration and tube formation than chADSCs in vitro. We confirmed that IL-6 siRNA significantly reduced the transcriptional level of IL-6 in obADSCs, thereby reducing the expression of vascular endothelial growth factor (VEGF)- A, VEGF receptor 2, transforming growth factor β, and Notch ligands and receptors in obADSCs.
The finding suggests that inflammatory cytokine interleukin-6 (IL-6) promotes the proangiogenic ability of obADSCs via the IL-6 signaling pathway.
肥胖的流行以及肥胖引起的慢性炎症性疾病在全球范围内都呈上升趋势。慢性炎症与血管生成的复杂过程有关，我们发现肥胖个体来源的脂肪干细胞（obADSCs）具有促血管生成的特征，包括更高水平的白细胞介素 6（IL-6）、Notch 配体和受体以及促血管生成细胞因子的表达，比对照受试者。我们假设 IL-6 和 Notch 信号通路对于调节 obADSCs 的促血管生成特征是必不可少的。
本研究旨在探讨炎症细胞因子白细胞介素 6（IL-6）是否通过 IL-6 信号通路促进肥胖个体脂肪干细胞的促血管生成能力。
我们比较了体外 ADSC 的表型分析以及细胞倍增时间、增殖、迁移、分化和促血管生成特性。此外，我们使用小干扰 RNA 抑制 IL-6 的基因和蛋白表达。
我们发现从对照个体（chADSCs）和 obADSCs 分离的 ADSC 具有相似的表型和生长特征，并且 chADSCs 比 obADSCs 具有更强的分化能力。然而，obADSCs 在体外比 chADSCs 更能促进 EA.hy926 细胞的迁移和管状形成。我们证实，IL-6 siRNA 显著降低了 obADSCs 中 IL-6 的转录水平，从而降低了 obADSCs 中血管内皮生长因子（VEGF）-A、VEGF 受体 2、转化生长因子 β 和 Notch 配体和受体的表达。
研究结果表明，炎症细胞因子白细胞介素 6（IL-6）通过 IL-6 信号通路促进肥胖个体来源的脂肪干细胞的促血管生成能力。
