MiR32-5p Promoted Vascular Smooth Muscle Cell Calcification by Upregulating TNFα in the Microenvironment

Overview

Journal BMC Immunol

Publisher Biomed Central

Specialty Allergy & Immunology

Date 2020 Jan 19

PMID 31952480

Citations 6

Authors

Jingsong Cao

Ling Chen

Xiaoling Zhong

Yingying Shen

Yan Gao

Qian Chen

Xuyu Zu

Jianghua Liu

Affiliations

Soon will be listed here.

Abstract

Background: Vascular calcification is often associated with chronic inflammation and is a risk factor for brain arterial stiffness. Our previous results showed that miR32-5p was positively correlated with vascular smooth muscle cells (VSMC) calcification, but it is unclear whether miR32-5p promoted VSMC calcification by regulating inflammatory factor production.

Results: In this study, bioinformatics analysis was used to select tumour necrosis factor α (TNFα) as a candidate inflammatory factor associated with calcification. Moreover, alizarin red staining and qRT-PCR analysis revealed that TNFα produced by BV2 cells was the key promoting factor of VSMC calcification. Interestingly, the expression of TNFα was significantly increased at the mRNA and protein levels after miR32-5p mimic treatment but significantly decreased after miR32-5p antagomir treatment. To explore the mechanism of the regulation of TNFα expression by miR32-5p, bioinformatics analysis indicated that PIKfyve was a candidate target gene of miR32-5p, and luciferase assays verified that the expression of PIKfyve was significantly repressed by miR32-5p mimics. Importantly, rescue experiments showed that the expression of TNFα in BV2 cells treated with miR32-5p antagomir and the PIKfyve inhibitor YM201636 was significantly increased.

Conclusions: The production of TNFα in microglia could be affected by miR32-5p targeting PIKfyve, and these results will be beneficial to reveal the mechanism of brain arterial calcification.

Citing Articles

Transglutaminase 2 regulates endothelial cell calcification via IL-6-mediated autophagy.

Liu B, Cai Z, Wang Y, Liu X, Zhang B, Zheng Q Front Pharmacol. 2024; 15:1393534.

PMID: 39654623 PMC: 11625581. DOI: 10.3389/fphar.2024.1393534.

Vascular Calcification: Molecular Networking, Pathological Implications and Translational Opportunities.

Ortega M, De Leon-Oliva D, Gimeno-Longas M, Boaru D, Fraile-Martinez O, Garcia-Montero C Biomolecules. 2024; 14(3).

PMID: 38540696 PMC: 10968665. DOI: 10.3390/biom14030275.

Pravastatin promotes type 2 diabetes vascular calcification through activating intestinal Bacteroides fragilis to induce macrophage M1 polarization.

Chen C, Liang Z, He Y, Li A, Gao Y, Pan Q J Diabetes. 2023; 16(6):e13514.

PMID: 38112268 PMC: 11128749. DOI: 10.1111/1753-0407.13514.

Extracellular vesicle miR-32 derived from macrophage promotes arterial calcification in mice with type 2 diabetes via inhibiting VSMC autophagy.

Cao J, Chen C, Chen Q, Gao Y, Zhao Z, Yuan Q J Transl Med. 2022; 20(1):307.

PMID: 35794619 PMC: 9258116. DOI: 10.1186/s12967-022-03502-8.

Magic and mystery of microRNA-32.

Zeng Z, Zhu Q, Zhao Z, Zu X, Liu J J Cell Mol Med. 2021; 25(18):8588-8601.

PMID: 34405957 PMC: 8435424. DOI: 10.1111/jcmm.16861.

References

Jackson A, Regine M, Subrata C, Long S . Molecular mechanisms and genetic regulation in atherosclerosis. Int J Cardiol Heart Vasc. 2018; 21:36-44. PMC: 6161413. DOI: 10.1016/j.ijcha.2018.09.006. View

Liu J, Xiao X, Shen Y, Chen L, Xu C, Zhao H . MicroRNA-32 promotes calcification in vascular smooth muscle cells: Implications as a novel marker for coronary artery calcification. PLoS One. 2017; 12(3):e0174138. PMC: 5358880. DOI: 10.1371/journal.pone.0174138. View

Aghagolzadeh P, Bachtler M, Bijarnia R, Jackson C, Smith E, Odermatt A . Calcification of vascular smooth muscle cells is induced by secondary calciprotein particles and enhanced by tumor necrosis factor-α. Atherosclerosis. 2016; 251:404-414. DOI: 10.1016/j.atherosclerosis.2016.05.044. View

Viegas C, Costa R, Santos L, Videira P, Silva Z, Araujo N . Gla-rich protein function as an anti-inflammatory agent in monocytes/macrophages: Implications for calcification-related chronic inflammatory diseases. PLoS One. 2017; 12(5):e0177829. PMC: 5436823. DOI: 10.1371/journal.pone.0177829. View

Dudink E, Florijn B, Weijs B, Duijs J, Luermans J, Peeters F . Vascular Calcification and not Arrhythmia in Idiopathic Atrial Fibrillation Associates with Sex Differences in Diabetic Microvascular Injury miRNA Profiles. Microrna. 2018; 8(2):127-134. DOI: 10.2174/2211536608666181122125208. View

Zhang C, Zhang K, Huang F, Feng W, Chen J, Zhang H . Exosomes, the message transporters in vascular calcification. J Cell Mol Med. 2018; 22(9):4024-4033. PMC: 6111818. DOI: 10.1111/jcmm.13692. View

Kwon D, Kim Y, Kook H . New Aspects of Vascular Calcification: Histone Deacetylases and Beyond. J Korean Med Sci. 2017; 32(11):1738-1748. PMC: 5639052. DOI: 10.3346/jkms.2017.32.11.1738. View

Leopold J . Vascular calcification: Mechanisms of vascular smooth muscle cell calcification. Trends Cardiovasc Med. 2014; 25(4):267-74. PMC: 4414672. DOI: 10.1016/j.tcm.2014.10.021. View

Sadekova N, Iulita M, Vallerand D, Muhire G, Bourmoum M, Claing A . Arterial stiffness induced by carotid calcification leads to cerebral gliosis mediated by oxidative stress. J Hypertens. 2017; 36(2):286-298. DOI: 10.1097/HJH.0000000000001557. View

10.

Hayashi K, Sasai M, Iwasaki A . Toll-like receptor 9 trafficking and signaling for type I interferons requires PIKfyve activity. Int Immunol. 2015; 27(9):435-45. PMC: 4560039. DOI: 10.1093/intimm/dxv021. View

11.

Ma Y, Shi Q, Xiao K, Wang J, Chen C, Gao L . Stimulations of the Culture Medium of Activated Microglia and TNF-Alpha on a Scrapie-Infected Cell Line Decrease the Cell Viability and Induce Marked Necroptosis That Also Occurs in the Brains from the Patients of Human Prion Diseases. ACS Chem Neurosci. 2018; 10(3):1273-1283. DOI: 10.1021/acschemneuro.8b00354. View

12.

Kawasaki T, Takemura N, Standley D, Akira S, Kawai T . The second messenger phosphatidylinositol-5-phosphate facilitates antiviral innate immune signaling. Cell Host Microbe. 2013; 14(2):148-58. DOI: 10.1016/j.chom.2013.07.011. View

13.

Pan Z, Lu Y, Yang B . MicroRNAs: a novel class of potential therapeutic targets for cardiovascular diseases. Acta Pharmacol Sin. 2009; 31(1):1-9. PMC: 4002691. DOI: 10.1038/aps.2009.175. View

14.

Bardeesi A, Gao J, Zhang K, Yu S, Wei M, Liu P . A novel role of cellular interactions in vascular calcification. J Transl Med. 2017; 15(1):95. PMC: 5414234. DOI: 10.1186/s12967-017-1190-z. View

15.

Kim G, Dayam R, Prashar A, Terebiznik M, Botelho R . PIKfyve inhibition interferes with phagosome and endosome maturation in macrophages. Traffic. 2014; 15(10):1143-63. DOI: 10.1111/tra.12199. View

16.

Fakhry M, Skafi N, Fayyad-Kazan M, Kobeissy F, Hamade E, Mebarek S . Characterization and assessment of potential microRNAs involved in phosphate-induced aortic calcification. J Cell Physiol. 2017; 233(5):4056-4067. DOI: 10.1002/jcp.26121. View

17.

Tronchere H, Cinato M, Timotin A, Guitou L, Villedieu C, Thibault H . Inhibition of PIKfyve prevents myocardial apoptosis and hypertrophy through activation of SIRT3 in obese mice. EMBO Mol Med. 2017; 9(6):770-785. PMC: 5452048. DOI: 10.15252/emmm.201607096. View

18.

Terajima M, Kaneko-Kobayashi Y, Nakamura N, Yuri M, Hiramoto M, Naitou M . Inhibition of c-Rel DNA binding is critical for the anti-inflammatory effects of novel PIKfyve inhibitor. Eur J Pharmacol. 2016; 780:93-105. DOI: 10.1016/j.ejphar.2016.03.036. View

19.

Nonoda Y, Saito Y, Itoh M, Nakagawa E, Sugai K, Takahashi A . Activation of microglia/macrophages expressing phosphorylated S6 ribosomal protein in a case of hemimegalencephaly with progressive calcification and atrophy. J Neurol Sci. 2009; 287(1-2):52-9. DOI: 10.1016/j.jns.2009.09.010. View

20.

Liu Y, Li M, Zhang Z, Ye Y, Zhou J . Role of microglia-neuron interactions in diabetic encephalopathy. Ageing Res Rev. 2017; 42:28-39. DOI: 10.1016/j.arr.2017.12.005. View