miR548ai antagonism attenuates exosome-induced endothelial cell dysfunction.
miR548ai antagonism attenuates exosome-induced endothelial cell dysfunction.
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DOI：
10.1038/s41420-021-00720-9
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发表时间：
2021-10-28
影响因子：
7
通讯作者：
Kent CK
中科院分区：
文献类型：
--
作者：
Xie X;Guo LW;Kent CK
内皮细胞（EC）和平滑肌细胞（SMC）是血管壁的主要相邻细胞类型。最近的研究表明，它们之间的通讯对于血管的稳态和发病机制至关重要。特别地，通过外来体的功能障碍（增殖）SMC可以诱导EC功能障碍（生长受损）。目前的研究表明，miR 548 ai，一种罕见的microRNA，可能提供了一个分子靶点，用于保护SMC/外泌体诱导的EC功能障碍。我们对不同细胞因子（PDGF-BB、TGFβ1、TNFα、IL 1 β）诱导的功能障碍的人主动脉SMC的microRNA进行了微阵列分析。在这些细胞因子通常上调的microRNA中，miR 548 ai显示出最稳健的变化，这也通过定量PCR验证。在SMC衍生的外来体microRNA的qPCR测定中重现了这种苦参碱诱导的miR 548 ai上调。与SMC到EC的通讯一致，从马槟榔碱刺激的SMC中提取的外泌体损害了人EC的增殖和迁移。特别令人感兴趣的是，这种SMC外泌体对EC的撞击通过将miR 548 ai抑制剂microRNA转染到EC中来抵消。此外，转染到SMC中的miR 548 ai抑制剂减弱SMC功能障碍/增殖。因此，这些结果将miR 548 ai鉴定为新靶标;即，miR 548 ai抑制剂减轻由源自功能失调的SMC的外来体诱导的EC功能失调。这一新知识可能有助于基于microRNA的血管疾病治疗的未来发展。
Endothelial cell (EC) and smooth muscle cell (SMC) are major cell types adjacent in the vascular wall. Recent progress indicates that their communication is crucial for vascular homeostasis and pathogenesis. In particular, dysfunctional (proliferative) SMCs through exosomes can induce EC dysfunction (impaired growth). The current study suggests that miR548ai, a rarely known microRNA, may provide a molecular target for protection against SMC/exosome-induced EC dysfunction. We performed microarray profiling of microRNAs of dysfunctional human primary aortic SMCs induced by different cytokines (PDGF-BB, TGFβ1, TNFα, IL1β). Among the microRNAs commonly upregulated by these cytokines, miR548ai showed the most robust changes, as also validated through quantitative PCR. This cytokine-induced miR548ai upregulation was recapitulated in the qPCR determination of SMC-derived exosomal microRNAs. Consistent with SMC-to-EC communication, the exosomes extracted from cytokine-stimulated SMCs impaired human EC proliferation and migration. Of particular interest, this SMC exosomal impingement on ECs was countered by transfection of miR548ai inhibitor microRNA into ECs. Furthermore, the miR548ai inhibitor transfected into SMCs attenuated SMC dysfunction/proliferation. Thus, these results identify miR548ai as a novel target; namely, miR548ai inhibitor mitigates EC dysfunction induced by exosomes derived from dysfunctional SMCs. This new knowledge may aid the future development of microRNA-based treatment of vascular disorders.
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影响因子：
3.1
作者：
Neerukonda, Sabari Nath;Egan, Nicholas A.;Parcells, Mark S.
通讯作者：
Parcells, Mark S.
DOI：
10.1161/atvbaha.116.308886
发表时间：
2017-03-01
影响因子：
8.7
作者：
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通讯作者：
Shanahan, Catherine M.
影响因子：
37.3
作者：
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通讯作者：
Marsit CJ
影响因子：
6
作者：
Heo, Jeongyeon;Yang, Hee Cheol;Kang, Hara
通讯作者：
Kang, Hara
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DOI：
10.1083/jcb.201110132
发表时间：
2012-06-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Lutter S;Xie S;Tatin F;Makinen T
通讯作者：
Makinen T