Liraglutide preserves CD34+ stem cells from dysfunction Induced by high glucose exposure

This record contains raw data related to the article "Liraglutide preserves CD34+ stem cells from dysfunction Induced by high glucose exposure" Background: Glucagon like peptide-1 receptor agonists (GLP-1RAs) have shown to reduce mortality and cardiovascular events in patients with type 2 diabetes mellitus (T2DM). Since the impairment in number and function of vasculotrophic circulating CD34+ hematopoietic stem progenitor cells (HSPCs) in T2D has been reported to increase cardiovascular (CV) risk, we hypothesized that one of the mechanisms whereby GLP-1 RAs exert CV protective effects may be related to the ability to improve CD34+ HSPC function. Methods: In cord blood (CB)-derived CD34+ HSPC, the expression of GLP-1 receptor (GLP-1R) mRNA, receptor protein and intracellular signaling was evaluated by RT-qPCR and Western Blot respectively. CD34+ HSPCs were exposed to high glucose (HG) condition and GLP-1RA liraglutide (LIRA) was added before as well as after functional impairment. Proliferation, CXCR4/SDF-1α axis activity and intracellular ROS production of CD34+ HSPC were evaluated. Results: CD34+ HSPCs express GLP-1R at transcriptional and protein level. LIRA treatment prevented and rescued HSPC proliferation, CXCR4/SDF-1α axis activity and metabolic imbalance from HG-induced impairment. LIRA stimulation promoted intracellular cAMP accumulation as well as ERK1/2 and AKT signaling activation. The selective GLP-1R antagonist exendin (9-39) abrogated LIRA-dependent ERK1/2 and AKT phosphorylation along with the related protective effects. Conclusion: We provided the first evidence that CD34+ HSPC express GLP-1R and that LIRA can favorably impact on cell dysfunction due to HG exposure. These findings open new perspectives on the favorable CV effects of GLP-1 RAs in T2DM patients. Keywords: CD34+ hematopoietic stem progenitor cells; Cardiovascular disease; GLP-1 receptor agonist; Type 2 diabetes mellitus. This dataset is not public. It’s available upon reasonable requesto to the corresponding author.本数据集包含与论文《利拉鲁肽可保护CD34+干细胞免受高糖暴露诱导的功能损伤》相关的原始数据。 背景：胰高血糖素样肽-1受体激动剂（GLP-1RAs）已被证实可降低2型糖尿病（T2DM）患者的死亡率与心血管事件发生率。已有研究表明，2型糖尿病患者体内血管营养性循环CD34+造血干祖细胞（HSPCs）的数量与功能受损会增加心血管（CV）风险，因此我们提出假说：GLP-1受体激动剂发挥心血管保护作用的潜在机制之一，可能与其改善CD34+造血干祖细胞功能的能力相关。 方法：本研究针对脐带血（CB）来源的CD34+造血干祖细胞，分别通过实时定量聚合酶链反应（RT-qPCR）与蛋白质印迹法（Western Blot）检测其GLP-1受体（GLP-1R）的mRNA表达、受体蛋白表达及细胞内信号通路激活情况。将CD34+造血干祖细胞置于高糖（HG）环境中培养，并在其功能受损前后加入GLP-1受体激动剂利拉鲁肽（LIRA）。随后检测CD34+造血干祖细胞的增殖能力、CXCR4/SDF-1α轴活性及细胞内活性氧（ROS）生成水平。 结果：CD34+造血干祖细胞在转录与蛋白水平均表达GLP-1受体。利拉鲁肽处理可预防并逆转高糖诱导的CD34+造血干祖细胞增殖受损、CXCR4/SDF-1α轴活性异常及代谢失衡。利拉鲁肽刺激可促进细胞内环磷酸腺苷（cAMP）积累，同时激活ERK1/2与AKT信号通路。选择性GLP-1受体拮抗剂艾塞那肽（9-39）可阻断利拉鲁肽介导的ERK1/2与AKT磷酸化，并抵消其相关保护作用。 结论：本研究首次证实CD34+造血干祖细胞表达GLP-1受体，且利拉鲁肽可有效改善高糖暴露诱导的细胞功能损伤。上述发现为GLP-1受体激动剂改善2型糖尿病患者心血管获益的机制提供了全新的研究视角。 关键词：CD34+造血干祖细胞；心血管疾病；GLP-1受体激动剂；2型糖尿病。 本数据集尚未公开，需经合理申请后向通讯作者获取。