HucMSCs can alleviate abnormal vasculogenesis induced by high glucose through the MAPK signaling pathway

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2024-11-09 DOI:10.1016/j.isci.2024.111354

Yang Yao , Tiantian Shan , Xiaoying Li

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Abstract

Vascular complications caused by diabetes mellitus contribute a major threat to increased disability and mortality of diabetic patients, which are characterized by damaged endothelial cells and angiogenesis. Human umbilical cord-derived mesenchymal stem cells (hucMSCs) have been demonstrated to alleviate endothelial cell damage and improve angiogenesis. However, these investigations overlooked the pivotal role of vasculogenesis. In this study, we utilized blood vessel organoids (BVOs) to investigate the impact of high glucose on vasculogenesis and subsequent angiogenesis. We found that BVOs in the vascular lineage induction stage were more sensitive to high glucose and more susceptible to affect endothelial cell differentiation and function. Moreover, hucMSCs can alleviate the high glucose-induced inhibition of endothelial cell differentiation and dysfunction through MAPK signaling pathway downregulation, with the MAPK activator dimethyl fumarate further illustrating the results. Thereby, we demonstrated that high glucose can lead to abnormal vasculogenesis and impact subsequent angiogenesis, and hucMSCs can alleviate this effect.

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HucMSCs 可通过 MAPK 信号通路缓解高糖诱导的异常血管生成

糖尿病引起的血管并发症是导致糖尿病患者残疾和死亡率增加的主要威胁，其特点是内皮细胞受损和血管生成。人类脐带间充质干细胞（hucMSCs）已被证明可减轻内皮细胞损伤并改善血管生成。然而，这些研究忽视了血管生成的关键作用。在本研究中，我们利用血管器官组织（BVOs）研究了高糖对血管生成和后续血管生成的影响。我们发现，处于血管系诱导阶段的 BVOs 对高糖更敏感，更容易影响内皮细胞的分化和功能。此外，hucMSCs 可通过下调 MAPK 信号通路缓解高糖诱导的内皮细胞分化抑制和功能障碍，MAPK 激活剂富马酸二甲酯进一步说明了这一结果。因此，我们证明了高血糖可导致血管生成异常并影响后续的血管生成，而 HucMSCs 可减轻这种影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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