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诱导生理机械拉伸下人主动脉平滑肌细胞中的基因表达调控

Gene expression modulation in human aortic smooth muscle cells under induced physiological mechanical stretch.

作者信息

Ben Hassine Amira, Petit Claudie, Thomas Mireille, Mundweiler Stéphanie, Guignandon Alain, Avril Stéphane

机构信息

Mines Saint-Etienne, Université Jean Monnet, INSERM, U 1059 SAINBIOSE, Saint-Etienne, 42023, France.

出版信息

Sci Rep. 2024 Dec 28;14(1):31147. doi: 10.1038/s41598-024-82495-4.

DOI:10.1038/s41598-024-82495-4
PMID:39732782
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11682279/
Abstract

In this study, we investigated gene expression in vitro of human primary Aortic smooth muscle cells (AoSMCs) in response to 9% physiological dynamic stretch over a 4 to 72-h timeframe using RT-qPCR. AoSMC were derived from primary culture and were exposed to continuous cycles of stretch and relaxation at 1 Hz by a computer-controlled Flex Jr.™ Tension System. Unstretched control AoSMCs were simultaneously cultured in the same dishes. Our results revealed a rapid and significant upregulation of specific genes (COL1A1, FBN1, LAMA5, TGFBR1 and TGFBR2) within the initial 4 h for AoSMCs subjected to dynamic stretching, whilst control cells did not respond within the same 4 h. The upregulated genes were the ones associated with extracellular matrix (ECM) fibrillogenesis and regulation of traction forces. Interestingly, stretched cells maintained stable gene expression between 4 and 72 h, whilst control cells exhibited variations over time in the absence of mechanical cues. These findings shed light on the essential role played by pulsatile stretches in the regulation of gene expressions by AoSMCs and the intricate processes governing their mechanobiological function, paving the way for further investigations in cardiovascular health.

摘要

在本研究中,我们使用逆转录定量聚合酶链反应(RT-qPCR),在4至72小时的时间范围内,研究了人原代主动脉平滑肌细胞(AoSMC)在9%生理动态拉伸刺激下的体外基因表达情况。AoSMC来源于原代培养,并通过计算机控制的Flex Jr.™张力系统,以1赫兹的频率暴露于连续的拉伸和松弛循环中。未拉伸的对照AoSMC同时在相同培养皿中培养。我们的结果显示,受到动态拉伸的AoSMC在最初4小时内,特定基因(COL1A1、FBN1、LAMA5、TGFBR1和TGFBR2)迅速且显著上调,而对照细胞在相同的4小时内没有反应。上调的基因是与细胞外基质(ECM)纤维形成和牵引力调节相关的基因。有趣的是,拉伸细胞在4至72小时内保持稳定的基因表达,而对照细胞在没有机械信号的情况下随时间表现出变化。这些发现揭示了搏动性拉伸在AoSMC基因表达调节中所起的重要作用,以及控制其力学生物学功能的复杂过程,为心血管健康的进一步研究铺平了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/055f/11682279/9e2f6998dc61/41598_2024_82495_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/055f/11682279/5a8e06b73a31/41598_2024_82495_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/055f/11682279/f0a9c427ad07/41598_2024_82495_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/055f/11682279/8980bc263366/41598_2024_82495_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/055f/11682279/9e2f6998dc61/41598_2024_82495_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/055f/11682279/5a8e06b73a31/41598_2024_82495_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/055f/11682279/f0a9c427ad07/41598_2024_82495_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/055f/11682279/8980bc263366/41598_2024_82495_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/055f/11682279/9e2f6998dc61/41598_2024_82495_Fig4_HTML.jpg

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