血小板衍生生长因子刺激的肺动脉平滑肌细胞通过细胞外小泡miR-409-5p调节肺动脉内皮细胞功能障碍。

IF 2.9 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Biological Chemistry Pub Date : 2023-10-31 Print Date: 2024-03-25 DOI:10.1515/hsz-2023-0222
Jeongyeon Heo, Hara Kang
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引用次数: 0

摘要

血小板衍生生长因子(PDGF)诱导的血管平滑肌细胞(VSMCs)变化刺激血管重塑,导致肺动脉高压等血管疾病。VSMCs通过携带货物(包括微小RNA)的细胞外小泡(EV)与内皮细胞通信。为了了解病理条件下PDGF刺激的肺动脉平滑肌细胞(PASMC)与肺动脉内皮细胞(PAEC)相互作用的分子机制,我们研究了PDGF刺激下PASMC和PAEC之间通过细胞外小泡miR-409-5p的串扰。miR-409-5p在PASMC中的表达在PDGF信号传导后上调,并释放到EV中。miR-409-5p的表达升高被转运到PAEC,并导致其功能受损,包括NO释放减少,从而导致PASMC增殖增强。我们认为PASMC细胞外小泡miR-409-5p-PAEC的正调控环是PDGF刺激下PASMC增殖的潜在机制。因此,miR-409-5p可能是治疗血管疾病的新靶点,包括肺动脉高压。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Platelet-derived growth factor-stimulated pulmonary artery smooth muscle cells regulate pulmonary artery endothelial cell dysfunction through extracellular vesicle miR-409-5p.

Platelet-derived growth factor (PDGF)-induced changes in vascular smooth muscle cells (VSMCs) stimulate vascular remodeling, resulting in vascular diseases such as pulmonary arterial hypertension. VSMCs communicate with endothelial cells through extracellular vesicles (EVs) carrying cargos, including microRNAs. To understand the molecular mechanisms through which PDGF-stimulated pulmonary artery smooth muscle cells (PASMCs) interact with pulmonary artery endothelial cells (PAECs) under pathological conditions, we investigated the crosstalk between PASMCs and PAECs via extracellular vesicle miR-409-5p under PDGF stimulation. miR-409-5p expression was upregulated in PASMCs upon PDGF signaling, and it was released into EVs. The elevated expression of miR-409-5p was transported to PAECs and led to their impaired function, including reduced NO release, which consequentially resulted in enhanced PASMC proliferation. We propose that the positive regulatory loop of PASMC-extracellular vesicle miR-409-5p-PAEC is a potential mechanism underlying the proliferation of PASMCs under PDGF stimulation. Therefore, miR-409-5p may be a novel therapeutic target for the treatment of vascular diseases, including pulmonary arterial hypertension.

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来源期刊
Biological Chemistry
Biological Chemistry 生物-生化与分子生物学
CiteScore
7.20
自引率
0.00%
发文量
63
审稿时长
4-8 weeks
期刊介绍: Biological Chemistry keeps you up-to-date with all new developments in the molecular life sciences. In addition to original research reports, authoritative reviews written by leading researchers in the field keep you informed about the latest advances in the molecular life sciences. Rapid, yet rigorous reviewing ensures fast access to recent research results of exceptional significance in the biological sciences. Papers are published in a "Just Accepted" format within approx.72 hours of acceptance.
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