MicroRNA‑132 promotes oxidative stress‑induced pyroptosis by targeting sirtuin 1 in myocardial ischaemia‑reperfusion injury

Zhou,Yan; Li,Kun‑Sheng; Liu,Lu; Li,Shi‑Liang

doi:10.3892/ijmm.2020.4557

MicroRNA‑132 promotes oxidative stress‑induced pyroptosis by targeting sirtuin 1 in myocardial ischaemia‑reperfusion injury

Authors:
- Yan Zhou
- Kun‑Sheng Li
- Lu Liu
- Shi‑Liang Li
View Affiliations

Affiliations: Department of Otolaryngology, Union Hospital, Tongji Medical College, Wuhan, Hubei 430000, P.R. China, Department of Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China, Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, P.R. China, Division of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, P.R. China
Published online on: March 30, 2020 https://doi.org/10.3892/ijmm.2020.4557
Pages: 1942-1950

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The present study aimed to investigate the roles of miR‑132 in myocardial ischaemia/reperfusion (I/R) injury and the underlying mechanisms. The myocardial I/R model was established using C57BL/J6 mice. Haematoxylin and eosin staining was performed to observe the injury of myocardial tissues. Commercial kits were used to measure the levels of serum myocardial enzymes and inflammatory factors. The in vitro I/R model was established by the hypoxia/reoxygenation method using H9C2 cells. A dual luciferase reporter assay was used to confirm the binding of miR‑132 and sirtuin 1 (SIRT1). Cell pyroptosis was determined using flow cytometry. Reverse transcription‑quantitative PCR was performed to determine the expression of miR‑132, SIRT1 and inflammatory factors. The levels of peroxisome proliferator‑activated receptor gamma coactivator (PGC)‑1α/nuclear factor erythroid‑2‑related factor 2 (Nrf2) signalling, oxidative stress and pyroptosis‑related proteins were detected by western blotting. Apparent histologic injury and elevated levels of serum myocardial enzymes and inflammatory factors were observed in the myocardial I/R model. miR‑132 was significantly upregulated and SIRT1 was markedly downregulated in I/R myocardial tissues. miR‑132 directly targeted SIRT1 and negatively regulated the expression of SIRT1. PGC‑1α, Nrf2, endothelial nitric oxide synthase and superoxide dismutase levels were significantly decreased, while inducible nitric oxide synthase and malondialdehyde levels were significantly increased by I/R induction. The pyroptosis‑related proteins NLRP3, caspase‑1 and interleukin (IL)‑1β were also significantly elevated by I/R induction. Inhibition of miR‑132 activated PGC‑1α/Nrf2 signalling and inhibited oxidative stress and the expression of the pyroptosis‑related proteins NLRP3, caspase‑1 and IL‑1β, which were all reversed by inhibiting SIRT1 with EX527. The findings of the present study indicated that inhibition of miR‑132 may ameliorate myocardial I/R injury by inhibiting oxidative stress and pyroptosis through activation of PGC‑1α/Nrf2 signalling by targeting SIRT1.

View Figures

View References

1	Yu P, Zhang J, Yu S, Luo Z, Hua F, Yuan L, Zhou Z, Liu Q, Du X, Chen S, et al: Protective effect of sevoflurane post-conditioning against cardiac ischemia/reperfusion injury via ameliorating mitochondrial impairment, oxidative stress and rescuing autophagic clearance. PLoS One. 10:e01346662015. View Article : Google Scholar
2	Pryds K, Nielsen RR, Jorsal A, Hansen MS, Ringgaard S, Refsgaard J, Kim WY, Petersen AK, Bøtker HE and Schmidt MR: Effect of long-term remote ischemic conditioning in patients with chronic ischemic heart failure. Basic Res Cardiol. 112:672017. View Article : Google Scholar : PubMed/NCBI
3	Dang M, Zeng X, Wang H, Li H, Du F and Chen B: GW28-e0833 Inhibition of myocardial ischemia/reperfusion apoptosis by soluble receptor for advanced glycation end-product (sRAGE) via interferon-induced immunoproteasome activity. J Am College Cardiol. 70:C31–C32. 2017. View Article : Google Scholar
4	Fabbri M, Croce CM and Calin GA: MicroRNAs. Cancer J. 14:759–774. 2015.
5	Bartel DP: MicroRNAs: Target recognition and regulatory functions. Cell. 136:215–233. 2009. View Article : Google Scholar : PubMed/NCBI
6	Xiao J, Zhu X, He B, Zhang Y, Kang B, Wang Z and Ni X: MiR-204 regulates cardiomyocyte autophagy induced by ischemia-reperfusion through LC3-II. J Biomedical Sci. 18:352011. View Article : Google Scholar
7	Pan Z, Sun X, Ren J, Li X, Gao X, Lu C, Zhang Y, Sun H, Wang Y, Wang H, et al: miR-1 exacerbates cardiac ischemia-reperfusion injury in mouse models. PLoS One. 7:e505152012. View Article : Google Scholar : PubMed/NCBI
8	Peng J, Omran A, Ashhab MU, Kong H, Gan N, He F and Yin F: Expression patterns of miR-124, miR-134, miR-132, and miR-21 in an immature rat model and children with mesial temporal lobe epilepsy. J Mol Neuroscience. 50:291–297. 2013. View Article : Google Scholar
9	Formosa A, Lena AM, Markert EK, Cortelli S, Miano R, Mauriello A, Croce N, Vandesompele J, Mestdagh P, Finazzi-Agrò E, et al: DNA methylation silences miR-132 in prostate cancer. Oncogene. 32:127–134. 2013. View Article : Google Scholar
10	Wei X, Tan C, Tang C, Ren G, Xiang T, Qiu Z, Liu R and Wu Z: Epigenetic repression of miR-132 expression by the hepatitis B virus x protein in hepatitis B virus-related hepatocellular carcinoma. Cell Signal. 25:1037–1043. 2013. View Article : Google Scholar : PubMed/NCBI
11	Hong S, Lee J, Seo HH, Lee CY, Yoo KJ, Kim SM, Lee S, Hwang KC and Choi E: Na(+)-Ca(2+) exchanger targeting miR-132 prevents apoptosis of cardiomyocytes under hypoxic condition by suppressing Ca(2+) overload. Biochem Biophys Res Commun. 460:931–937. 2015. View Article : Google Scholar : PubMed/NCBI
12	Keasey MP, Scott HL, Bantounas I, Uney JB and Kelly S: MiR-132 is upregulated by ischemic preconditioning of cultured hippocampal neurons and protects them from subsequent OGD toxicity. J Mol Neurosci. 59:404–410. 2016. View Article : Google Scholar : PubMed/NCBI
13	Qu H, Lin K, Wang H, Wei H, Ji B, Yang Z, Peng C, Xiao X and Deng H: 1,25(OH)Dimproves cardiac dysfunction, hypertrophy, and fibrosis through PARP1/SIRT1/mTOR-related mechanisms in type 1 diabetes. Mol Nutr Food Res. 61:2017. View Article : Google Scholar
14	Shah SA, Khan M, Jo MH, Min GJ, Amin FU and Kim MO: Melatonin stimulates the SIRT1/Nrf2 signaling pathway counteracting lipopolysaccharide (LPS)-induced oxidative stress to rescue postnatal rat brain. CNS Neurosci Ther. 23:33–44. 2017. View Article : Google Scholar
15	Huang K, Gao X and Wei W: The crosstalk between Sirt1 and Keap1/Nrf2/ARE anti-oxidative pathway forms a positive feedback loop to inhibit FN and TGF β1 expressions in rat glomerular mesangial cells. Exp Cell Res. 361:632017. View Article : Google Scholar : PubMed/NCBI
16	Wang X, Yuan B, Cheng B, Liu Y, Zhang B, Wang X, Lin X, Yang B and Gong G: Crocin alleviates myocardial ischemia/reperfusion-induced endoplasmic reticulum stress via regulation of MIR-34A/SIRT1/NRF2 Pathway. Shock. 51:123–130. 2019. View Article : Google Scholar
17	Dal Bo M, D’Agaro T, Gobessi S, Zucchetto A, Dereani S, Rossi D, Zaja F, Pozzato G, Di Raimondo F, Gaidano G, et al: The SIRT1/TP53 axis is activated upon B-cell receptor triggering via miR-132 up-regulation in chronic lymphocytic leukemia cells. Oncotarget. 6:19102–19117. 2015. View Article : Google Scholar : PubMed/NCBI
18	Hadar A, Milanesi E, Walczak M, Puzianowskakuźnicka M, Kuźnicki J, Squassina A, Niola P, Chillotti C, Attems J, Gozes I and Gurwitz D: SIRT1, miR-132 and miR-212 link human longevity to Alzheimer’s Disease. Sci Rep. 8:84652018. View Article : Google Scholar
19	Bergsbaken T, Fink SL and Cookson BT: Pyroptosis: Host cell death and inflammation. Nat Rev Microbiol. 7:99–109. 2009. View Article : Google Scholar : PubMed/NCBI
20	Vande Walle L and Lamkanfi M: Pyroptosis. Curr Biol. 26:R568–R572. 2016. View Article : Google Scholar : PubMed/NCBI
21	Kim JY, Paton JC, Briles DE, Rhee DK and Pyo S: Streptococcus pneumoniaeinduces pyroptosis through the regulation of autophagy in murine microglia. Oncotarget. 6:44161–44178. 2015. View Article : Google Scholar : PubMed/NCBI
22	Li R, Zhang LM and Sun WB: Erythropoietin rescues primary rat cortical neurons from pyroptosis and apoptosis via Erk1/2-Nrf2/Bach1 signal pathway. Brain Res Bull. 130:236–244. 2017. View Article : Google Scholar : PubMed/NCBI
23	Han Z, Cao J, Song D, Tian L, Chen K, Wang Y, Gao L, Yin Z, Fan Y and Wang C: Autophagy is involved in the cardioprotection effect of remote limb ischemic postconditioning on myocardial ischemia/Reperfusion injury in normal mice, but not diabetic mice. PLoS One. 9:e868382014. View Article : Google Scholar : PubMed/NCBI
24	Wei LF, Zhang HM, Wang SS, Jing JJ, Zheng ZC, Gao JX, Liu Z and Tian J: Changes of MDA and SOD in brain tissue after secondary brain injury with seawater immersion in rats. Turk Neurosurg. 26:384–288. 2016.PubMed/NCBI
25	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar
26	He B, Xiao J, Ren AJ, Zhang YF, Zhang H, Chen M, Xie B, Gao XG and Wang YW: Role of miR-1 and miR-133a in myocardial ischemic postconditioning. J Biomed Sci. 18:222011. View Article : Google Scholar : PubMed/NCBI
27	Li H, Liao Y, Gao L, Zhuang T, Huang Z, Zhu H and Ge J: Coronary serum exosomes derived from patients with myocardial ischemia regulate angiogenesis through the, 2018 miR-939-mediated Nitric Oxide Signaling Pathway. Theranostics. 8:2079–2093. 2018. View Article : Google Scholar :
28	Smith PY, Hernandez-Rapp J, Jolivette F, Lecours C, Bisht K, Goupil C, Dorval V, Parsi S, Morin F, Planel E, et al: miR-132/212 deficiency impairs tau metabolism and promotes pathological aggregation in vivo. Hum Mol Genet. 24:6721–6735. 2015. View Article : Google Scholar : PubMed/NCBI
29	You J, Li Y, Fang N, Liu B, Zu L, Chang R, Li X and Zhou Q: MiR-132 suppresses the migration and invasion of lung cancer cells via targeting the EMT regulator ZEB2. PLoS One. 9:e918272014. View Article : Google Scholar : PubMed/NCBI
30	Huang W, Liang J, Ashraf A, Xu M, Millard RW, Ashraf M and Wang Y: Abstract 9990: Regulation of miR132 in cardiac fibroblasts after ischemia enhances angiogenesis and reduction of apoptosis by targeting sonic hedgehog. Circulation. 124:A99902011.
31	Hsu CP, Zhai P, Yamamoto T, Maejima Y, Matsushima S, Hariharan N, Shao D, Takagi H, Oka S and Sadoshima J: Sirt1 protects the heart from ischemia/reperfusion. Circulation. 122:2170–2182. 2011. View Article : Google Scholar
32	Fan H, Yang HC, You L, Wang YY, He WJ and Hao CM: The histone deacetylase, SIRT1, contributes to the resistance of young mice to ischemia/reperfusion-induced acute kidney injury. Kidney Int. 83:404–413. 2013. View Article : Google Scholar : PubMed/NCBI
33	Yu L, Sun Y, Cheng L, Jin Z, Yang Y, Zhai M, Pei H, Wang X, Zhang H, Meng Q, et al: Melatonin receptor-mediated protection against myocardial ischemia/reperfusion injury: Role of SIRT1. J Pineal Res. 57:228–238. 2015. View Article : Google Scholar
34	Ding M, Lei J, Han H, Li W, Qu Y, Fu E, Fu F and Wang X: SIRT1 protects against myocardial ischemia-reperfusion injury via activating eNOS in diabetic rats. Cardiovasc Diabetol. 14:1432015. View Article : Google Scholar : PubMed/NCBI
35	Miyazaki Y, Li R, Rezk A, Misirliyan H, Moore C, Farooqi N, Solis M, Goiry LG, de Faria Junior O, Dang VD, et al: A novel microRNA-132-surtuin-1 axis underlies aberrant B-cell cytokine regulation in patients with relapsing-remitting multiple sclerosis [corrected]. PLoS One. 9:e1054212014. View Article : Google Scholar
36	Xiong Y, Shi L, Wang L, Zhou Z, Wang C, Lin Y, Luo D, Qiu J and Chen D: Activation of sirtuin 1 by catalpol-induced downregulation of microRNA-132 attenuates endoplasmic reticulum stress in colitis. Pharmacol Res. 123:73–82. 2017. View Article : Google Scholar : PubMed/NCBI
37	Pan H, He M, Liu R, Brecha NC, Yu AC and Pu M: Sulforaphane protects rodent retinas against ischemia-reperfusion injury through the activation of the Nrf2/HO-1 antioxidant pathway. PLoS One. 9:e1141862014. View Article : Google Scholar : PubMed/NCBI
38	Chung SD, Lai TY, Chien CT and Yu HJ: Activating Nrf-2 signaling depresses unilateral ureteral obstruction-evoked mitochondrial stress-related autophagy, apoptosis and pyroptosis in kidney. PLoS One. 7:e472992012. View Article : Google Scholar : PubMed/NCBI