Login Register Cart 0
Generic placeholder image

Current Neurovascular Research

Editor-in-Chief

ISSN (Print): 1567-2026
ISSN (Online): 1875-5739

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Dual Specificity Phosphatase 3 (DUSP3) Knockdown Alleviates Acute Myocardial Infarction Damage via Inhibiting Apoptosis and Inflammation

Author(s): Aixia Jiang, Caixia Zhao, Dongying Zhang and Kun Yu*

Volume 20, Issue 1, 2023

Published on: 09 May, 2023

Page: [14 - 22] Pages: 9

DOI: 10.2174/1567202620666230502115433

Price: $65

Abstract

Background: Dual Specificity Phosphatase 3 (DUSP3) regulates the innate immune response and is associated with ischemia/reperfusion (I/R). However, the precise function of DUSP3 in acute myocardial infarction (AMI) remains to be established.

Methods: In this study, the AMI model in vivo was established in mice by permanent left anterior descending coronary artery (LAD) occlusion, and primary neonatal mouse cardiomyocytes were treated with hypoxia for 12 hours to mimic AMI in vitro. Sh-DUSP3 and AAV9-sh-DUSP3 were used to knock down the DUSP3 expression. LVEF%, LVFS%, SOD1, and HO-1 level, and TTC staining were used to test the cardiac function. Flow cytometric analysis, Western blot, and TUNEL staining were used to investigate the effect of DUSP3 knockdown on apoptosis. Moreover, we detect inflammatory factors expression and oxidative stress by ELISA. Besides, we investigate DUSP3 expression by RT-qPCR.

Results: Our findings determined the role of DUSP3 in the progression of AMI. And demonstrated that DUSP3 knockdown alleviated oxidative stress, inflammation, and apoptosis. In addition, our results indicated that DUSP3 knockdown could regulate the expression of p-NF-κB, ICAM1, and VCAM1.

Conclusion: Our results demonstrated that the knockdown of DUSP3 could effectively alleviate AMI symptoms and be mediated through the NF-κB signaling pathway.

« Previous Next »
[1]
Li X, Zhou J, Huang K. Inhibition of the lncRNA Mirt1 attenuates acute myocardial infarction by suppressing nf-κb activation. Cell Physiol Biochem 2017; 42(3): 1153-64.
[http://dx.doi.org/10.1159/000478870] [PMID: 28668956]
[2]
Cai Y, Xie KL, Wu HL, Wu K. Functional suppression of epiregulin impairs angiogenesis and aggravates left ventricular remodeling by disrupting the extracellular‐signal‐regulated kinase1/2 signaling pathway in rats after acute myocardial infarction. J Cell Physiol 2019; 234(10): 18653-65.
[http://dx.doi.org/10.1002/jcp.28503] [PMID: 31062344]
[3]
Yuan X, Pan J, Wen L, et al. MiR‐590‐3p regulates proliferation, migration and collagen synthesis of cardiac fibroblast by targeting ZEB1. J Cell Mol Med 2020; 24(1): 227-37.
[http://dx.doi.org/10.1111/jcmm.14704] [PMID: 31675172]
[4]
Shu L, Zhang W, Huang C, Huang G, Su G, Xu J. lncRNA ANRIL protects H9c2 cells against hypoxia‐induced injury through targeting the miR‐7‐5p/SIRT1 axis. J Cell Physiol 2020; 235(2): 1175-83.
[http://dx.doi.org/10.1002/jcp.29031] [PMID: 31264206]
[5]
Gong X, Zhu Y, Chang H, Li Y, Ma F. Long noncoding RNA MALAT1 promotes cardiomyocyte apoptosis after myocardial infarction via targeting miR-144-3p. Biosci Rep 2019; 39(8): BSR20191103.
[http://dx.doi.org/10.1042/BSR20191103] [PMID: 31227612]
[6]
Li J, Li X, Wang Q, et al. ST-segment elevation myocardial infarction in China from 2001 to 2011 (the China PEACE-Retrospective Acute Myocardial Infarction Study): A retrospective analysis of hospital data. Lancet 2015; 385(9966): 441-51.
[http://dx.doi.org/10.1016/S0140-6736(14)60921-1] [PMID: 24969506]
[7]
Anderson JL, Morrow DA. Acute myocardial infarction. N Engl J Med 2017; 376(21): 2053-64.
[http://dx.doi.org/10.1056/NEJMra1606915] [PMID: 28538121]
[8]
Heusch G, Gersh BJ. The pathophysiology of acute myocardial infarction and strategies of protection beyond reperfusion: A continual challenge. Eur Heart J 2016; 38(11): ehw224.
[http://dx.doi.org/10.1093/eurheartj/ehw224] [PMID: 27354052]
[9]
Thiele H, Akin I, Sandri M, et al. PCI strategies in patients with acute myocardial infarction and cardiogenic shock. N Engl J Med 2017; 377(25): 2419-32.
[http://dx.doi.org/10.1056/NEJMoa1710261] [PMID: 29083953]
[10]
Yousuf T, Nakhle A, Rawal H, Harrison D, Maini R, Irimpen A. Natural disasters and acute myocardial infarction. Prog Cardiovasc Dis 2020; 63(4): 510-7.
[http://dx.doi.org/10.1016/j.pcad.2020.05.003] [PMID: 32417189]
[11]
Jiang W, Xu C, Xu S, Su W, Du C, Dong J. Macrophage-derived, LRG1-enriched extracellular vesicles exacerbate aristolochic acid nephropathy in a TGFbetaR1-dependent manner. Cell Biol Toxicol 2021; 38(4): 629-48.
[http://dx.doi.org/10.1007/s10565-021-09666-1] [PMID: 34677723]
[12]
Schumacher MA, Todd JL, Rice AE, Tanner KG, Denu JM. Structural basis for the recognition of a bisphosphorylated MAP kinase peptide by human VHR protein Phosphatase. Biochemistry 2002; 41(9): 3009-17.
[http://dx.doi.org/10.1021/bi015799l] [PMID: 11863439]
[13]
Huang CY, Tan TH. DUSPs, to MAP kinases and beyond. Cell Biosci 2012; 2(1): 24.
[http://dx.doi.org/10.1186/2045-3701-2-24] [PMID: 22769588]
[14]
Wang JY, Yeh CL, Chou HC, et al. Vaccinia H1-related phosphatase is a phosphatase of ErbB receptors and is down-regulated in non-small cell lung cancer. J Biol Chem 2011; 286(12): 10177-84.
[http://dx.doi.org/10.1074/jbc.M110.163295] [PMID: 21262974]
[15]
Li JP, Yang CY, Chuang HC, et al. The phosphatase JKAP/DUSP22 inhibits T-cell receptor signalling and autoimmunity by inactivating Lck. Nat Commun 2014; 5(1): 3618.
[http://dx.doi.org/10.1038/ncomms4618] [PMID: 24714587]
[16]
Gallegos LL, Ng MR, Sowa ME, et al. A protein interaction map for cell-cell adhesion regulators identifies DUSP23 as a novel phosphatase for β-catenin. Sci Rep 2016; 6(1): 27114.
[http://dx.doi.org/10.1038/srep27114] [PMID: 27255161]
[17]
Khbouz B, Rowart P, Poma L, et al. The genetic deletion of the Dual Specificity Phosphatase 3 (DUSP3) attenuates kidney damage and inflammation following ischaemia/reperfusion injury in mouse. Acta Physiol 2022; 234(2): e13735.
[http://dx.doi.org/10.1111/apha.13735] [PMID: 34704357]
[18]
Singh P, Dejager L, Amand M, et al. DUSP3 genetic deletion confers M2-like macrophage–dependent tolerance to septic shock. J Immunol 2015; 194(10): 4951-62.
[http://dx.doi.org/10.4049/jimmunol.1402431] [PMID: 25876765]
[19]
Chen SJ, Wu P, Sun LJ, et al. miR-204 regulates epithelial-mesenchymal transition by targeting SP1 in the tubular epithelial cells after acute kidney injury induced by ischemia-reperfusion. Oncol Rep 2017; 37(2): 1148-58.
[http://dx.doi.org/10.3892/or.2016.5294] [PMID: 27959449]
[20]
Wang W, Sai WL, Yang B. [The role of macrophage polarization and interaction with renal tubular epithelial cells in ischemia-reperfusion induced acute kidney injury]. Sheng Li Xue Bao 2022; 74(1): 28-38.
[PMID: 35199123]
[21]
Roth GA, Johnson C, Abajobir A, et al. Global, regional, and national burden of cardiovascular diseases for 10 causes, 1990 to 2015. J Am Coll Cardiol 2017; 70(1): 1-25.
[http://dx.doi.org/10.1016/j.jacc.2017.04.052] [PMID: 28527533]
[22]
Gao E, Koch WJ. A novel and efficient model of coronary artery ligation in the mouse. Methods Mol Biol 2013; 1037: 299-311.
[http://dx.doi.org/10.1007/978-1-62703-505-7_17] [PMID: 24029943]
[23]
Bourron O, Le Bouc Y, Berard L, et al. Impact of age-adjusted insulin-like growth factor 1 on major cardiovascular events after acute myocardial infarction: Results from the fast-MI registry. J Clin Endocrinol Metab 2015; 100(5): 1879-86.
[http://dx.doi.org/10.1210/jc.2014-3968] [PMID: 25699636]
[24]
Li X, Chen YY, Wang XM, et al. Image-guided stem cells with functionalized self-assembling peptide nanofibers for treatment of acute myocardial infarction in a mouse model. Am J Transl Res 2017; 9(8): 3723-31.
[PMID: 28861163]
[25]
Chen T, Zhang N, Wang H, Hu S, Geng X. Knockdown of circROBO2 attenuates acute myocardial infarction through regulating the miR-1184/TRADD axis. Mol Med 2021; 27(1): 21.
[http://dx.doi.org/10.1186/s10020-021-00275-6] [PMID: 33658002]
[26]
Zhai C, Qian G, Wu H, et al. Knockdown of circ_0060745 alleviates acute myocardial infarction by suppressing NF‐κB activation. J Cell Mol Med 2020; 24(21): 12401-10.
[http://dx.doi.org/10.1111/jcmm.15748] [PMID: 32977365]
[27]
Hao L, ElShamy WM. BRCA1-IRIS activates cyclin D1 expression in breast cancer cells by downregulating the JNK phosphatase DUSP3/VHR. Int J Cancer 2007; 121(1): 39-46.
[http://dx.doi.org/10.1002/ijc.22597] [PMID: 17278098]
[28]
Wagner KW, Alam H, Dhar SS, et al. KDM2A promotes lung tumorigenesis by epigenetically enhancing ERK1/2 signaling. J Clin Invest 2013; 123(12): 5231-46.
[http://dx.doi.org/10.1172/JCI68642] [PMID: 24200691]
[29]
Pavic K, Duan G, Köhn M. VHR / DUSP 3 phosphatase: Structure, function and regulation. FEBS J 2015; 282(10): 1871-90.
[http://dx.doi.org/10.1111/febs.13263] [PMID: 25757426]
[30]
Alonso A, Saxena M, Williams S, Mustelin T. Inhibitory role for dual specificity phosphatase VHR in T cell antigen receptor and CD28-induced Erk and Jnk activation. J Biol Chem 2001; 276(7): 4766-71.
[http://dx.doi.org/10.1074/jbc.M006497200] [PMID: 11085983]
[31]
Amand M, Erpicum C, Bajou K, et al. DUSP3/VHR is a proangiogenic atypical dual-specificity phosphatase. Mol Cancer 2014; 13(1): 108.
[http://dx.doi.org/10.1186/1476-4598-13-108] [PMID: 24886454]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy