GAS5 knockdown suppresses inflammation and oxidative stress induced by oxidized low-density lipoprotein in macrophages b
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GAS5 knockdown suppresses inflammation and oxidative stress induced by oxidized low‑density lipoprotein in macrophages by sponging miR‑135a Yunyan Zhang1 · Xianben Lu1 · Minjun Yang1 · Jiaolin Shangguan1 · Yanping Yin1 Received: 2 August 2020 / Accepted: 23 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract A large number of long non-coding RNAs have been confirmed to play vital roles in regulating various biological processes. Abnormal expression of growth arrest-specific transcript 5 (GAS5) is reported to be involved in the development of atherosclerosis (AS). This work is to explore the detailed mechanism underling how GAS5 regulates AS progression. We found that the abundance of GAS5 was markedly increased, and miR-135a was decreased in AS patient serums and ox-LDL-induced human THP-1 cells dose and time dependently. Interference of GAS5 suppressed inflammation and oxidative stress induced by ox-LDL in THP-1 cells. Mechanistically, GAS5 acted as a molecular sponge of microRNA-135a (miR-135a). Rescue assays indicated that knockdown of miR-135a partially rescued small interference RNA for GAS5-inhibited inflammatory cytokines release and oxidative stress in ox-LDL-triggered THP-1 cells. In conclusion, the absence of GAS5-inhibited inflammatory response and oxidative stress induced by ox-LDL in THP-1 cells via sponging miR-135a, providing a deep insight into the molecular target for AS treatment. Keywords LncRNA · GAS5 · Atherosclerosis · miR-135a · Inflammation · Oxidative Stress
Introduction Atherosclerosis (AS) is a type of chronic inflammatory disease responsible for the occurrence of various vascular diseases [1]. To date, AS has become a significant health threat due to the increased morbidity and mortality worldwide. As a systemic disease, a large number of associated risk factors, like smoking, alcohol abuse, insulin resistance, hyperuricemia, and dyslipidemia, trigger the occurrence and development of AS. Recently, growing research suggests that the dysfunction of endothelial cells (ECs) and macrophages are the major mediators for AS onset [2, 3]. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11010-020-03962-w) contains supplementary material, which is available to authorized users. * Yanping Yin [email protected] 1
Department of Pathology, Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong University, No.150, Old Town Street, Linhai, Zhejiang, China
Oxidized low-density lipoprotein (ox-LDL) taken up by macrophages contributes to foam cell formation and lipid accumulation by inducing oxidative stress and inflammatory responses [4, 5]. Thus, comprehensive elucidation of the molecular mechanism on macrophage inflammation and oxidative stress derived by ox-LDL is imperative for improving the therapeutic effectiveness of AS patients. Long non-coding RNAs (lncRNAs), a class of conserved non-coding RNAs with more than 200 nucleotides in length, have been identified as vital regulator
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