GNAQ p.R183Q Endothelial Cells Fail to Align in Response to Laminar Shear Stress and Exhibit Increased Expression of MAPK, Inflammation, and Cell Adhesion Genes

IF 4.2 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Sana Nasim, Biju Issac, Qianyi Ma, Liang Sun, Joyce Bischoff
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Abstract

Vascular malformations are caused by germline or somatic mutations. A key research focus is the influence of laminar shear stress (LSS) on the development of these malformations. In this study, we explore how endothelial cells (EC) with the GNAQ p.R183Q somatic mutation, which is found in 90% of syndromic and non-syndromic capillary malformations (CM), respond to increasing levels of LSS. Our findings show that in contrast to control EC (EC-WT), the mutant EC (EC-R183Q) fail to align under LSS conditions. RNA sequencing revealed altered gene expression in EC-R183Q exposed to LSS, specifically in pathways related to MAPK, apoptosis, inflammation, and cell adhesion. These results suggest impaired mechanosensory responses in GNAQ p.R183Q endothelium that may contribute to vascular dysfunction in CM.

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GNAQ p.R183Q内皮细胞对层流剪切应力的反应不一致,并表现出MAPK,炎症和细胞粘附基因的表达增加
血管畸形是由种系或体细胞突变引起的。一个关键的研究重点是层流剪切应力(LSS)对这些畸形发展的影响。在这项研究中,我们探讨了GNAQ p.R183Q体细胞突变的内皮细胞(EC)如何对LSS水平的增加做出反应,这种突变在90%的综合征和非综合征性毛细血管畸形(CM)中发现。我们的研究结果表明,与对照EC (EC- wt)相比,突变EC (EC- r183q)在LSS条件下无法对准。RNA测序显示,暴露于LSS的EC-R183Q基因表达发生改变,特别是与MAPK、凋亡、炎症和细胞粘附相关的通路。这些结果提示GNAQ p.R183Q内皮的机械感觉反应受损可能导致CM的血管功能障碍。
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来源期刊
The FASEB Journal
The FASEB Journal 生物-生化与分子生物学
CiteScore
9.20
自引率
2.10%
发文量
6243
审稿时长
3 months
期刊介绍: The FASEB Journal publishes international, transdisciplinary research covering all fields of biology at every level of organization: atomic, molecular, cell, tissue, organ, organismic and population. While the journal strives to include research that cuts across the biological sciences, it also considers submissions that lie within one field, but may have implications for other fields as well. The journal seeks to publish basic and translational research, but also welcomes reports of pre-clinical and early clinical research. In addition to research, review, and hypothesis submissions, The FASEB Journal also seeks perspectives, commentaries, book reviews, and similar content related to the life sciences in its Up Front section.
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