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SRGN, a new identified shear-stress-responsive gene in endothelial cells

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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.

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Funding

This research program was supported by grants from the National Natural Science Foundation of China (31971242), Fundamental Research Funds for Central Universities (2019CDYGZD008, 2019CDXYSG0004), and Chongqing Science and Technology Bureau (cstc2019jcyj-zdxm0033) are gratefully acknowledged.

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Author notes

  1. Qinfeng Ma and Wei Gu contributed equally to this work and should be considered co-first authors.

Authors and Affiliations

  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

    Qinfeng Ma, Tianhan Li, Kun Zhang, Yuliang Cui, Kai Qu, Juhui Qiu & Guixue Wang

  2. School of Medicine, Faculty of Medicine, Chongqing University, Chongqing, China

    Wei Gu

  3. The Nanoscience Centre, University of Cambridge, Cambridge, CB3 0FF, UK

    Nan Wang, Rose Humphry & Colm Durkan

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  1. Qinfeng Ma
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  2. Wei Gu
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  3. Tianhan Li
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Contributions

QM, GW, JQ and WG contributed to the study conception and design. QM conducted the experiments and analyzed data, TL, KZ, KQ, YC helped to complete the partial experiments and data analysis. QM, WG, GW, JQ wrote the manuscript with input from all others. NW, CD, RH provided for invaluable discussion, editorial assistance and language polishing. GW provided research grants and approved the manuscript.

Corresponding authors

Correspondence to Juhui Qiu or Guixue Wang.

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The authors declare that they have no competing interests.

Ethical approval

The animal experiments were approved by the Laboratory Animal Welfare and Ethics Committee of the Third Military Medical University (project identification code SYXK-PLA-20170005, on 5 March 2019, Chongqing, China).

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Ma, Q., Gu, W., Li, T. et al. SRGN, a new identified shear-stress-responsive gene in endothelial cells. Mol Cell Biochem 474, 15–26 (2020). https://doi.org/10.1007/s11010-020-03830-7

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