SRGN , a new identified shear-stress-responsive gene in endothelial cells
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SRGN, a new identified shear‑stress‑responsive gene in endothelial cells Qinfeng Ma1 · Wei Gu2 · Tianhan Li1 · Kun Zhang1 · Yuliang Cui1 · Kai Qu1 · Nan Wang3 · Rose Humphry3 · Colm Durkan3 · Juhui Qiu1 · Guixue Wang1 Received: 12 February 2020 / Accepted: 11 July 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Endothelial cells (ECs) play an important role in the pathogenesis of cardiovascular disease, especially atherosclerosis (AS). The abnormal wall shear stress (WSS) which directly contacts with ECs is the key stimulating factor leading to AS. However, the underlying mechanism of ECs responding to WSS is still incompletely understood. This study aims to explore the novel mechano-sensitive genes and its potential mechanism in response to WSS in ECs by employing bioinformatics methods based on previously available high-throughput data from zebrafish embryos, both before and after blood flow formation. Six common differentially expressed genes (DEGs) (SRGN, SLC12A3, SLC25A4, PVALB1, ITGAE.2, zgc:198419) were selected out from two high-throughput datasets (GSE126617 and GSE20707) in the GEO database. Among them, SRGN was chosen for further verification through the in vitro shear stress loading experiments with human umbilical vein endothelial cells (HUVECs) and the in vivo partial ligation of carotid artery in mice. Our data indicated that low shear stress (LSS) could enhance the expression of SRGN via the PKA/CREB-dependent signaling pathway. The proportion of Ki67+ cells and the concentration of nitric oxide (NO) were high in SRGN high expression cells, suggesting that SRGN may be involved in the proliferation of HUVECs. Furthermore, in the partial ligation of the carotid artery mice model, we observed that the expression of SRGN was significantly increased in atherosclerotic plaques induced by abnormal shear stress. Taken together, this study demonstrated that SRGN is a key gene in the response of ECs to WSS and could be involved in AS. Keywords SRGN · Endothelial cells · Shear stress · Bioinformatics · Atherosclerosis
Introduction Qinfeng Ma and Wei Gu contributed equally to this work and should be considered co-first authors. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11010-020-03830-7) contains supplementary material, which is available to authorized users. * Juhui Qiu [email protected] * Guixue Wang [email protected] 1
Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Faculty of Medicine, Bioengineering College, Chongqing University, Chongqing 400030, China
2
School of Medicine, Faculty of Medicine, Chongqing University, Chongqing, China
3
The Nanoscience Centre, University of Cambridge, Cambridge CB3 0FF, UK
Endothelial cells (ECs) constitute the inner surface of vessels, which is the barrier between blood and the vessel wall in the physiological environment. Impairment of vascular endothelial barri
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