血管壁微环境:由偶然性纤维细胞分泌的外体诱导血管化
Ming-Hui Zheng1, Su-Kang Shan1, Xiao Lin2
1Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, the Second Xiangya Hospital, Central South University, Changsha, 410000, China.
Journal of nanobiotechnology
|September 4, 2023
概括
高诱导偶然性纤维细胞释放含有miR-21-5p的外体. 这些外体在慢性功能衰竭中促进血管化,通过降低血管光滑肌肉细胞中Crim1表达的调节.
科学领域:
- 血管生物学 血管生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 血管化是慢性功能衰竭 (CRF) 的重要并发症,增加心血管事件风险.
- 进发性纤维细胞 (AFs) 在血管壁微环境中发挥作用,影响血管光滑肌细胞 (VSMC) 化.
- 以前的研究强调了内皮细胞 (ECs) 和VSMCs之间的交叉声,以及调节VSMC化的近效应.
研究的目的:
- 调查高诱导AFs (AFsHPi-Exos) 在VSMC化中分泌的外体的作用.
- 阐明AF衍生的外体细胞作用在高血管壁微环境中的潜在机制.
- 为了确定参与AF介导的血管化中的特定分子参与者.
主要方法:
- 用高 (HPi) 诱导AF,并收集条件化介质和外体.
- 用条件介质和AFsHPi-Exos处理VSMC,评估化.
- 使用GW4869.9抑制外体生物发生/释放.
- 在AFsHPi-Exos中对miR-21-5p丰富的量化.
- 通过向Crim1.1,评估miR-21-5p对VSMC骨质性分化的影响.
- 在体内研究中,使用CRF小鼠接受AFsHPi-Exos或AFsmiR21M-Exos的治疗.
主要成果:
- 来自HPi诱导的AFs的条件介质促进了VSMC化,部分被GW4869.9阻止.
- AFsHPi-Exos模仿了条件介质的促进化的效果.
- miR-21-5p被丰富在AFs-HPi-Exos中,并通过降低Crim1.1的调节促进了VSMC骨质生成差异化.
- 在CRF小鼠中,AFsHPi-Exos和AFsmiR21M-Exos加速了血管化.
结论:
- 由高诱导的偶然性纤维细胞分泌的外体促进VSMC化.
- 该机制涉及通过外体传递miR-21-5p,导致VSMC中Crim1表达的下调.
- 这些发现凸显了AF衍生的外体和miR-21-5p在慢性功能衰竭和血管壁微环境的背景下在血管化中的关键作用.
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