BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

miR-328-5p functions as a critical negative regulator in early endothelial inflammation and advanced atherosclerosis

  • Yangxia Zhang (Henan Joint International Research Laboratory of Stem Cell Medicine, School of Medical Engineering, Xinxiang Medical University) ;
  • Yingke Li (Henan Joint International Research Laboratory of Stem Cell Medicine, School of Medical Engineering, Xinxiang Medical University) ;
  • Zhisheng Han (Henan Joint International Research Laboratory of Stem Cell Medicine, School of Medical Engineering, Xinxiang Medical University) ;
  • Qingyang Huo (Henan Joint International Research Laboratory of Stem Cell Medicine, School of Medical Engineering, Xinxiang Medical University) ;
  • Longkai Ji (Henan Joint International Research Laboratory of Stem Cell Medicine, School of Medical Engineering, Xinxiang Medical University) ;
  • Xuejia Liu (Stem Cells and Biotherapy Engineering Research Center of Henan, College of Life Science and Technology, Xinxiang Medical University) ;
  • Han Li (Stem Cells and Biotherapy Engineering Research Center of Henan, College of Life Science and Technology, Xinxiang Medical University) ;
  • Xinxing Zhu (Henan Joint International Research Laboratory of Stem Cell Medicine, School of Medical Engineering, Xinxiang Medical University) ;
  • Zhipeng Hao (Department of Thoracic Surgery of Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology)
  • Received : 2024.04.10
  • Accepted : 2024.06.10
  • Published : 2024.08.31
Download PDF
⟨ Previous Next ⟩

Abstract

Early proatherogenic inflammation constitutes a significant risk factor for atherogenesis development. Despite this, the precise molecular mechanisms driving this pathological progression largely remain elusive. Our study unveils a pivotal role for the microRNA miR-328-5p in dampening endothelial inflammation by modulating the stability of JUNB (JunB proto-oncogene). Perturbation of miR-328-5p levels results in heightened monocyte adhesion to endothelial cells and enhanced transendothelial migration, while its overexpression mitigates these inflammatory processes. Furthermore, miR-328-5p hinders macrophage polarization toward the pro-inflammatory M1 phenotype, and exerts a negative influence on atherosclerotic plaque formation in vivo. By pinpointing JUNB as a direct miR-328-5p target, our research underscores the potential of miR-328-5p as a therapeutic target for inflammatory atherosclerosis. Reintroduction of JUNB effectively counteracts the anti-atherosclerotic effects of miR-328-5p, highlighting the promise of pharmacological miR-328-5p targeting in managing inflammatory atherosclerosis.

Keywords

Acknowledgement

This work was supported by grants from the National Natural Science Foundation of China (81900392), Henan Outstanding Youth Science Fund (202300410307), Xinxiang Medical University Doctor Support Foundation (300-505307, XYBSKYZZ 201902), Graduate Research Innovation Support Program (YJSCX202206Z).

References

  1. Skalen K, Gustafsson M, Rydberg EK et al (2002) Subendothelial retention of atherogenic lipoproteins in early atherosclerosis. Nature 417, 750-754  https://doi.org/10.1038/nature00804
  2. Stachowicz A, Wisniewska A, Kus K et al (2019) The Influence of trehalose on atherosclerosis and hepatic steatosis in apolipoprotein E knockout mice. Int J Mol Sci 20, 1552 
  3. Vergallo R and Crea F (2020) Atherosclerotic plaque healing. N Engl J Med 383, 846-857  https://doi.org/10.1056/NEJMra2000317
  4. Yang ZH, Pryor M, Noguchi A et al (2019) Dietary palmitoleic acid attenuates atherosclerosis progression and hyperlipidemia in low-density lipoprotein receptor-deficient mice. Mol Nutr Food Res 63, e1900120 
  5. Choi BJ, Matsuo Y, Aoki T et al (2014) Coronary endothelial dysfunction is associated with inflammation and vasa vasorum proliferation in patients with early atherosclerosis. Arterioscl Throm Vas 34, 2473-2477  https://doi.org/10.1161/ATVBAHA.114.304445
  6. Feaver RE, Gelfand BD, Wang C, Schwartz MA and Blackman BR (2010) Atheroprone hemodynamics regulate fibronectin deposition to create positive feedback that sustains endothelial inflammation. Circ Res 106, 1703-1711  https://doi.org/10.1161/CIRCRESAHA.109.216283
  7. Evans TD, Jeong SJ, Zhang X, Sergin I and Razani B (2018) TFEB and trehalose drive the macrophage autophagy-lysosome system to protect against atherosclerosis. Autophagy 14, 724-726  https://doi.org/10.1080/15548627.2018.1434373
  8. Peled M and Fisher EA (2014) Dynamic aspects of macrophage polarization during atherosclerosis progression and regression. Front Immunol 5, 579 
  9. Wang Y, Wang GZ, Rabinovitch PS and Tabas I (2014) Macrophage mitochondrial oxidative stress promotes atherosclerosis and nuclear factor-κB-mediated inflammation in macrophages. Circ Res 114, 421-433  https://doi.org/10.1161/CIRCRESAHA.114.302153
  10. Yurdagul A, Doran AC, Cai B, Fredman G and Tabas IA (2017) Mechanisms and consequences of defective efferocytosis in atherosclerosis. Front Cardiovasc Med 4, 86 
  11. Fontana MF, Baccarella A, Pancholi N, Pufall MA, Herbert DBR and Kim CC (2015) JUNB is a key transcriptional modulator of macrophage activation. J Immunol 194, 177-186  https://doi.org/10.4049/jimmunol.1401595
  12. Xiao C, Wang RH, Lahusen TJ et al (2012) Progression of chronic liver inflammation and fibrosis driven by activation of c-JUN signaling in Sirt6 mutant mice. J Biol Chem 287, 41903-41913  https://doi.org/10.1074/jbc.M112.415182
  13. Hao XZ and Fan HM (2017) Identification of miRNAs as atherosclerosis biomarkers and functional role of miR-126 in atherosclerosis progression through MAPK signalling pathway. Eur Rev Med Pharmacol Sci 21, 2725-2733 
  14. Hirschberger S, Hinske LC and Kreth S (2018) MiRNAs: dynamic regulators of immune cell functions in inflammation and cancer. Cancer Lett 431, 11-21  https://doi.org/10.1016/j.canlet.2018.05.020
  15. Kim JM, Jung KH, Chu K et al (2015) Atherosclerosis-related circulating MicroRNAs as a predictor of stroke recurrence. Transl Stroke Res 6, 191-197  https://doi.org/10.1007/s12975-015-0390-1
  16. Olivieri F, Prattichizzo F, Giuliani A et al (2021) miR-21 and miR-146a: the microRNAs of inflammaging and age-related diseases. Ageing Res Rev 70, 101374 
  17. Quintavalle M, Condorelli G and Elia L (2011) Arterial remodeling and atherosclerosis: miRNAs involvement. Vascul Pharmacol 55, 106-110  https://doi.org/10.1016/j.vph.2011.08.216
  18. Krol J, Loedige I and Filipowicz W (2010) The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet 11, 597-610  https://doi.org/10.1038/nrg2843
  19. Lulla AR, Slifker MJ, Zhou Y et al (2017) miR-6883 Family miRNAs target CDK4/6 to induce G(1) phase cell-cycle arrest in colon cancer cells. Cancer Res 77, 6902-6913  https://doi.org/10.1158/0008-5472.CAN-17-1767
  20. Sherrard R, Luehr S, Holzkamp H, McJunkin K, Memar N and Conradt B (2017) miRNAs cooperate in apoptosis regulation during C. elegans development. Genes Dev 31, 209-222  https://doi.org/10.1101/gad.288555.116
  21. Zhao Y, Ponnusamy M, Dong Y, Zhang L, Wang K and Li P (2017) Effects of miRNAs on myocardial apoptosis by modulating mitochondria related proteins. Clin Exp Pharmacol Physiol 44, 431-440  https://doi.org/10.1111/1440-1681.12720
  22. Bushati N and Cohen SM (2007) microRNA functions. Annu Rev Cell Dev Biol 23, 175-205  https://doi.org/10.1146/annurev.cellbio.23.090506.123406
  23. Wu CY, Zhou ZF, Wang B, Ke ZP, Ge ZC and Zhang XJ (2019) MicroRNA-328 ameliorates oxidized low-density lipoprotein-induced endothelial cells injury through targeting HMGB1 in atherosclerosis. J Cell Biochem 120, 1643-1650  https://doi.org/10.1002/jcb.27469
  24. Binesh A, Devaraj SN and Devaraj H (2020) Expression of chemokines in macrophage polarization and downregulation of NFκB in aorta allow macrophage polarization by diosgenin in atherosclerosis. J Biochem Mol Toxic 34, e22422 https://doi.org/10.1002/jbt.22422
  25. Tabas I and Bornfeldt KE (2016) Macrophage phenotype and function in different stages of atherosclerosis. Circ Res 118, 653-667  https://doi.org/10.1161/CIRCRESAHA.115.306256
  26. Raife TJ, Dwyre DM, Stevens JW et al (2011) Human thrombomodulin knock-in mice reveal differential effects of human thrombomodulin on thrombosis and atherosclerosis. Arterioscler Thromb Vasc Biol 31, 2509-2517  https://doi.org/10.1161/ATVBAHA.111.236828
  27. Shankman LS, Gomez D, Cherepanova OA et al (2015) KLF4-dependent phenotypic modulation of smooth muscle cells has a key role in atherosclerotic plaque pathogenesis. Nat Med 21, 628-637  https://doi.org/10.1038/nm.3866
  28. Takaya T, Hirata K, Yamashita T et al (2007) A specific role for eNOS-derived reactive oxygen species in atherosclerosis progression. Arterioscler Thromb Vasc Biol 27, 1632-1637  https://doi.org/10.1161/ATVBAHA.107.142182
  29. Khoyratty TE, Ai Z, Ballesteros I et al (2021) Distinct transcription factor networks control neutrophil-driven inflammation. Nat Immunol 22, 1093-1106  https://doi.org/10.1038/s41590-021-00968-4
  30. Mathas S, Hinz M, Anagnostopoulos I et al (2002) Aberrantly expressed c-Jun and JunB are a hallmark of Hodgkin lymphoma cells, stimulate proliferation and synergize with NF-kappa B. EMBO J 21, 4104-4113  https://doi.org/10.1093/emboj/cdf389
  31. Schmidt D, Textor B, Pein OT et al (2007) Critical role for NF-kappaB-induced JunB in VEGF regulation and tumor angiogenesis. EMBO J 26, 710-719 https://doi.org/10.1038/sj.emboj.7601539