Skip to main content
Log in

MicroRNA-29b-3p Targets SPARC Gene to Protect Cardiocytes against Autophagy and Apoptosis in Hypoxic-Induced H9c2 Cells

  • Original Article
  • Published:
Journal of Cardiovascular Translational Research Aims and scope Submit manuscript

Abstract

MicroRNAs participate in the regulation of abnormal cardiomyocyte apoptosis and autophagy, which leads to heart failure (HF). Lower miR-29b-3p levels were found in HF patients in this study. However, the role of miR-29b-3p in the molecular pathogenesis of HF remains unclear. Hypoxia-stimulated H9c2 cells were used an in vitro model of HF. It was found that hypoxia stimulation decreased the miR-29b-3p expression and enhanced cell apoptosis and autophagy response in H9c2 cells. While the effects of hypoxia on cell apoptosis and autophagy were reversed by miR-29b-3p transfection, especially 100 nM. The secreted protein acidic and rich in cysteine (SPARC), predicted as a direct target of miR-29b-3p, aggravated the hypoxia-induced cells apoptosis, autophagy, and TGFβ1/Smad3 activation. While the changes were dramatically reversed by miR-29b-3p. Taken together, our data suggest that miR-29b-3p plays an important role in the progression of HF through targeting SPARC and regulating TGFβ1/Smad3 pathway.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Brito D., Cepeda B. (2017) Heart failure, congestive (CHF).

  2. Jose Corbalan, J., Vatner, D. E., & Vatner, S. F. (2016). Myocardial apoptosis in heart disease: does the emperor have clothes? Basic Research in Cardiology, 111(3), 31.

    Article  CAS  PubMed  Google Scholar 

  3. Xia, P., Liu, Y., & Cheng, Z. (2016). Signaling pathways in cardiac myocyte apoptosis. BioMed Research International, 2016, 9583268.

    PubMed  PubMed Central  Google Scholar 

  4. Gustafsson, A. B., & Gottlieb, R. A. (2009). Autophagy in ischemic heart disease. Circulation Research, 104(2), 150–158.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Mialet-Perez, J., & Vindis, C. (2017). Autophagy in health and disease: focus on the cardiovascular system. Essays in Biochemistry, 61(6), 721–732.

    Article  PubMed  Google Scholar 

  6. Wong, L. L., Rademaker, M. T., Saw, E. L., Lew, K. S., Ellmers, L. J., Charles, C. J., Richards, A. M., & Wang, P. (2017). Identification of novel microRNAs in the sheep heart and their regulation in heart failure. Scientific Reports, 7(1), 8250.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Tijsen, A. J., Pinto, Y. M., & Creemers, E. E. (2012). Non-cardiomyocyte microRNAs in heart failure. Cardiovascular Research, 93(4), 573–582.

    Article  CAS  PubMed  Google Scholar 

  8. Mendell, J. T., & Olson, E. N. (2012). MicroRNAs in stress signaling and human disease. Cell, 148(6), 1172–1187.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Zhu, M. L., Yin, Y. L., Ping, S., Yu, H. Y., Wan, G. R., Jian, X., & Li, P. (2017). Berberine promotes ischemia-induced angiogenesis in mice heart via upregulation of microRNA-29b. Clinical and Experimental Hypertension, 39(7), 672–679.

    Article  CAS  PubMed  Google Scholar 

  10. Yang, F., Li, P., Li, H., Shi, Q., Li, S., & Zhao, L. (2015). microRNA-29b mediates the antifibrotic effect of Tanshinone IIA in postinfarct cardiac remodeling. Journal of Cardiovascular Pharmacology, 65(5), 456–464.

    Article  CAS  PubMed  Google Scholar 

  11. Abonnenc, M., Nabeebaccus, A. A., Mayr, U., Barallobre-Barreiro, J., Dong, X., Cuello, F., Sur, S., Drozdov, I., Langley, S. R., Lu, R., et al. (2013). Extracellular matrix secretion by cardiac fibroblasts: role of microRNA-29b and microRNA-30c. Circulation Research, 113(10), 1138–1147.

    Article  CAS  PubMed  Google Scholar 

  12. Marques, F. Z., Vizi, D., Khammy, O., Mariani, J. A., & Kaye, D. M. (2016). The transcardiac gradient of cardio-microRNAs in the failing heart. European Journal of Heart Failure, 18(8), 1000–1008.

    Article  CAS  PubMed  Google Scholar 

  13. Yang, Y. F., Wu, C. C., Chen, W. P., & Su, M. J. (2009). Transforming growth factor-beta type I receptor/ALK5 contributes to doxazosin-induced apoptosis in H9C2 cells. Naunyn-Schmiedeberg’s Archives of Pharmacology, 380(6), 561–567.

    Article  CAS  PubMed  Google Scholar 

  14. Ghavami, S., Cunnington, R. H., Gupta, S., Yeganeh, B., Filomeno, K. L., Freed, D. H., Chen, S., Klonisch, T., Halayko, A. J., Ambrose, E., et al. (2015). Autophagy is a regulator of TGF-beta1-induced fibrogenesis in primary human atrial myofibroblasts. Cell Death & Disease, 6, e1696.

    Article  CAS  Google Scholar 

  15. Chen, K., Chen, W., Liu, S. L., Wu, T. S., Yu, K. F., Qi, J., Wang, Y., Yao, H., Huang, X. Y., Han, Y., et al. (2018). Epigallocatechingallate attenuates myocardial injury in a mouse model of heart failure through TGFbeta1/Smad3 signaling pathway. Molecular Medicine Reports, 17(6), 7652–7660.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Pandey, A. C., Lancaster, J. J., Harris, D. T., Goldman, S., & Juneman, E. (2017). Cellular therapeutics for heart failure: focus on mesenchymal stem cells. Stem Cells International, 2017, 9640108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Hashimoto, H., Olson, E. N., & Bassel-Duby, R. (2018). Therapeutic approaches for cardiac regeneration and repair. Nature Reviews. Cardiology.

  18. Zhang, J., Liu, D., Zhang, M., & Zhang, Y. (2018). Cardiomyocyte programmed necrosis: mitochondria, death receptor and beyond. Br J Pharmacol.

  19. Moon, S. H., Bae, D., Jung, T. H., Chung, E. B., Jeong, Y. H., Park, S. J., & Chung, H. M. (2017). From bench to market: preparing human pluripotent stem cells derived cardiomyocytes for various applications. Int J Stem Cells, 10(1), 1–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Huang, Z., Ye, B., Dai, Z., Wu, X., Lu, Z., Shan, P., & Huang, W. (2015). Curcumin inhibits autophagy and apoptosis in hypoxia/reoxygenation-induced myocytes. Molecular Medicine Reports, 11(6), 4678–4684.

    Article  CAS  PubMed  Google Scholar 

  21. Qin, L., Fan, S., Jia, R., & Liu, Y. (2018). Ginsenoside Rg1 protects cardiomyocytes from hypoxia-induced injury through the PI3K/AKT/mTOR pathway. Pharmazie, 73(6), 349–355.

    CAS  PubMed  Google Scholar 

  22. Roohbakhsh, A., Shamsizadeh, A., Hayes, A. W., Reiter, R. J., & Karimi, G. (2018). Melatonin as an endogenous regulator of diseases: the role of autophagy. Pharmacological Research.

  23. Kriegel, A. J., Liu, Y., Fang, Y., Ding, X., & Liang, M. (2012). The miR-29 family: genomics, cell biology, and relevance to renal and cardiovascular injury. Physiological Genomics, 44(4), 237–244.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ye, Y., Hu, Z., Lin, Y., Zhang, C., & Perez-Polo, J. R. (2010). Downregulation of microRNA-29 by antisense inhibitors and a PPAR-gamma agonist protects against myocardial ischaemia-reperfusion injury. Cardiovascular Research, 87(3), 535–544.

    Article  CAS  PubMed  Google Scholar 

  25. Zhang, J., He, Z., Xiao, W., Na, Q., Wu, T., Su, K., & Cui, X. (2016). Overexpression of BAG3 attenuates hypoxia-induced cardiomyocyte apoptosis by inducing autophagy. Cellular Physiology and Biochemistry, 39(2), 491–500.

    Article  CAS  PubMed  Google Scholar 

  26. Mehrhof, F. B., Muller, F. U., Bergmann, M. W., Li, P., Wang, Y., Schmitz, W., Dietz, R., & von Harsdorf, R. (2001). In cardiomyocyte hypoxia, insulin-like growth factor-I-induced antiapoptotic signaling requires phosphatidylinositol-3-OH-kinase-dependent and mitogen-activated protein kinase-dependent activation of the transcription factor cAMP response element-binding protein. Circulation, 104(17), 2088–2094.

    Article  CAS  PubMed  Google Scholar 

  27. Hu, Z., Cai, H. Y., Luo, Y. Y., Xiao, J. M., Li, L., & Guo, T. (2018). Effect of varying hypoxia reoxygenation times on autophagy of cardiomyocytes. Acta Cirúrgica Brasileira, 33(3), 223–230.

    Article  PubMed  Google Scholar 

  28. Harris, B. S., Zhang, Y., Card, L., Rivera, L. B., Brekken, R. A., & Bradshaw, A. D. (2011). SPARC regulates collagen interaction with cardiac fibroblast cell surfaces. American Journal of Physiology. Heart and Circulatory Physiology, 301(3), H841–H847.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Hartley, P. S., Motamedchaboki, K., Bodmer, R., & Ocorr, K. (2016). SPARC-dependent cardiomyopathy in drosophila. Circulation. Cardiovascular Genetics, 9(2), 119–129.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Lindsey, M. L., Mann, D. L., Entman, M. L., & Spinale, F. G. (2003). Extracellular matrix remodeling following myocardial injury. Annals of Medicine, 35(5), 316–326.

    Article  CAS  PubMed  Google Scholar 

  31. Wang, Y., Wang, Q., Zhang, L., Ke, Z., Zhao, Y., Wang, D., Chen, H., Jiang, X., Gu, M., Fan, S., et al. (2017). Coptisine protects cardiomyocyte against hypoxia/reoxygenation-induced damage via inhibition of autophagy. Biochemical and Biophysical Research Communications, 490(2), 231–238.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to thank the members of the Second Department of Cardiology, Xinxiang Central Hospital for participating and providing blood samples in this study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yan Wang.

Ethics declarations

Conflict of Interest

The author declares that they have no conflicts of interest.

Human Subjects/Informed Consent Statement

The present study was approved by the Ethics Committee of Xinxiang Central Hospital, and written informed consent was obtained from the patients and healthy donors.

Animal Studies

No animal studies were carried out by the authors for this article.

Additional information

Associate Editor Joost Sluijter oversaw the review of this article

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhou, S., Lei, D., Bu, F. et al. MicroRNA-29b-3p Targets SPARC Gene to Protect Cardiocytes against Autophagy and Apoptosis in Hypoxic-Induced H9c2 Cells. J. of Cardiovasc. Trans. Res. 12, 358–365 (2019). https://doi.org/10.1007/s12265-018-9858-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12265-018-9858-1

Keywords

Navigation