R&D Center for Tailor-Made QOL, University of Tsukuba, Tsukuba, Japan.
Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba, Japan.
J Cell Mol Med. 2021 Aug;25(15):7229-7243. doi: 10.1111/jcmm.16752. Epub 2021 Jun 27.
Anaemia is one of the leading causes of disability in young adults and is associated with increased morbidity and mortality in elderly. With a global target to reduce the disease burden of anaemia, recent researches focus on novel compounds with the ability to induce erythropoiesis and regulate iron homeostasis. We aimed to explore the biological events and potential polypharmacological effects of water-extracted olive leaf (WOL) on human bone marrow-derived haematopoietic stem cells (hHSCs) using a comprehensive gene expression analysis. HPLC analysis identifies six bioactive polyphenols in the WOL. Treatment with WOL for 12 days regulated gene expressions related to erythroid differentiation, oxygen homeostasis, iron homeostasis, haem metabolism and Hb biosynthesis in hHSCs. Functional clustering analysis reveals several major functions of WOL such as ribosomal biogenesis and mitochondrial translation machinery, glycolytic process, ATP biosynthesis and immune response. Additionally, the colonies of both primitive and mature erythroid progenitors, CFU-E and BFU-E, were significantly increased in WOL-treated hHSCs. The expressions of erythroid markers, CD47, glycophorin A (GYPA), and transferrin receptor (TFRC) and adult Hb subunits-HBA and HBB were also confirmed in immunofluorescent staining and flow cytometer analysis in WOL-treated hHSCs. It is well known that induction of lineage-specific differentiation, as well as the maturation of early haematopoietic precursors into fully mature erythrocytes, involves multiple simultaneous biological events and complex signalling networks. In this regard, our genome-wide transcriptome profiling with microarray study on WOL-treated hHSCs provides general insights into the multitarget prophylactic and/or therapeutic potential of WOL in anaemia and other haematological disorders.
贫血是导致年轻人残疾的主要原因之一，与老年人发病率和死亡率的增加有关。随着全球减少贫血疾病负担的目标，最近的研究集中在具有诱导红细胞生成和调节铁平衡能力的新型化合物上。我们旨在使用全面的基因表达分析探索水提橄榄叶（WOL）对人骨髓源性造血干细胞（hHSCs）的生物学事件和潜在多效性作用。HPLC 分析鉴定出 WOL 中的六种生物活性多酚。用 WOL 处理 12 天可调节 hHSCs 中与红细胞分化、氧平衡、铁平衡、血红素代谢和 Hb 生物合成相关的基因表达。功能聚类分析揭示了 WOL 的几个主要功能，如核糖体生物发生和线粒体翻译机制、糖酵解过程、ATP 生物合成和免疫反应。此外，WOL 处理的 hHSCs 中原始和成熟红细胞祖细胞（CFU-E 和 BFU-E）的集落也显著增加。在 WOL 处理的 hHSCs 中，免疫荧光染色和流式细胞仪分析也证实了红细胞标记物 CD47、糖蛋白 A（GYPA）和转铁蛋白受体（TFRC）以及成人 Hb 亚基-HBA 和 HBB 的表达。众所周知，诱导谱系特异性分化以及早期造血前体细胞向完全成熟红细胞的成熟涉及多个同时发生的生物学事件和复杂的信号网络。在这方面，我们对 WOL 处理的 hHSCs 进行了全基因组转录组微阵列研究，为 WOL 在贫血和其他血液疾病中的多靶点预防和/或治疗潜力提供了一般见解。
