MicroRNA-137 protects burn-induced myocardial depression via regulation of the Notch signaling pathway

AJBM crossMark

Justin Sambol¹, Jordi Horton¹, Hong Chen², Nasser ghaly Yousif³, Catalina Gonzales¹, Jack Faulkner¹*


Clinical and experimental evidence shows myocardial contractile depression develops 4-24 hrs post-burn. Although the pathogenesis responsible for burn-induced myocardial depression is not well known, the aim of study is to investigate the role of microRNA-34a (miR-34a) in myocardial injury following post-burn by targeting Notch signaling pathway. MicroRNAs (miRNAs) have emerged as novel regulators in various pathological processes, but the precise role of miRNAs in post burn-induced myocardial depression remains largely unknown, a model of burn procedure. The results showed that for the first time that MicroRNA-137 functionally regulates Notch signaling pathway to protect burn-induced myocardial injury. Therefore, dual targeting of both the MicroRNA-137 and Notch1 signaling axes may be a potential therapeutic avenue to inhibit the burn-induced myocardial injury.

Keywords: MicroRNA-137; Notch; Burn-induced myocardial depression

Copyright © 2016 Faulkner J et al This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Article citationReferencesFull-Text/PDFFeedback
The citation data is computed by the following citation measuring services:

Google scholarcitedby


  1. Jarriault S, Brou C, Logeat F, Schroeter EH, Kopan R, Israel A. Signalling downstream of activated mammalian Notch. Nature 1995;377:355-358.
  2. Schroeter EH, Kisslinger JA, Kopan R. Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain. Nature 1998;393:382-386.
  3. Jarriault S, Le Bail O, Hirsinger E, et al. Delta-1 activation of notch-1 signaling results in HES-1 transactivation. Mol Cell Biol 1998;18:7423-7431.
    PMid:9819428 PMCid:PMC109323
  4. Lawson ND, Vogel AM, Weinstein BM. Sonic hedgehog and vascular endothelial growth factor act upstream of the Notch pathway during arterial endothelial differentiation. Dev Cell 2002;3:127-136.
  5. Krebs LT, Xue Y, Norton CR, et al. Notch signaling is essential for vascular morphogenesis in mice.Genes Dev 2000;14:1343-1352.
    PMid:10837027 PMCid:PMC316662
  6. Artavanis-Tsakonas S, Rand MD, Lake RJ. Notch signaling: cell fate control and signal integration in development. Science 1999;284:770-776.
  7. Alexiou P, Maragkakis M, Papadopoulos GL, Reczko M, Hatzigeorgiou AG. Lost in translation: an assessment and perspective for computational microRNA target identification. Bioinformatics 2009;25:3049-3055.
  8. Alvarez-Saavedra E, Horvitz HR. Many families of C. elegans microRNAs are not essential for development or viability. Current Biol 2010;20:367-373.
    PMid:20096582 PMCid:PMC2844791
  9. Ameres SL, Horwich MD, Hung JH, Xu J, Ghildiyal M, Weng Z, Zamore PD. Target RNA-directed trimming and tailing of small silencing RNAs. Science 2010;328:1534-1539.
    PMid:20558712 PMCid:PMC2902985
  10. Conlon RA, Reaume AG, Rossant J. Notch1 is required for the coordinate segmentation of somites. Development 1995;121:1533-1545.
  11. Yousif NG, AL-Amran FG. Novel Toll-like receptor-4 deficiency attenuates trastuzumab (Herceptin) induced cardiac injury in mice. BMC Cardiovascular Disorders 2011:11:62. https://doi.org/10.1186/1471-2261-11-62.
  12. Murohara T, Asahara T, Silver M, et al. Nitric oxide synthase modulates angiogenesis in response to tissue ischemia. J Clin Invest 1998;101:2567-2578.
    PMid:9616228 PMCid:PMC508846
  13. Arroyo JD, Chevillet JR, Kroh EM, et al. Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci USA 2011;108:5003-5008.
    PMid:21383194 PMCid:PMC3064324
  14. Wu L, Lu L, Goldowitz D, Williams RW, Cui Y. PolymiRTS Database: linking polymorphisms in microRNA target sites with complex traits. Nucleic Acids Res 2007;35:D51-54.
  15. Yin K J, Olsen K, Hamblin M, Zhang ., Schwendeman SP, Chen YE. Vascular endothelial cell-specific MicroRNA-15a inhibits angiogenesis in hindlimb ischemia. Journal of Biological Chemistry 2012;287(32):27055–27064.
    PMid:22692216 PMCid:PMC3411046
  16. Chamorro-Jorganes A, Araldi E, Penalva L OF, Sandhu D, Fernández-Hernando C, Suárez Y. MicroRNA-16 and MicroRNA-424 regulate cell-autonomous angiogenic functions in endothelial cells via targeting vascular endothelial growth factor receptor-2 and fibroblast growth factor receptor-1. Arteriosclerosis, Thrombosis, and Vascular Biology 2011;31(11):2595–2606.
    PMid:21885851 PMCid:PMC3226744
  17. Wang XH, Qian RZ, Zhang W, Chen SF, Jin HM, Hu RM. MicroRNA-320 expression in myocardial microvascular endothelial cells and its relationship with insulin-like growth factor-1 in type 2 diabetic rats. Clinical and Experimental Pharmacology & Physiology. 2009;36(2):181–188.
  18. Wang X, Huang W, Liu G, et al. Cardiomyocytes mediate anti-angiogenesis in type 2 diabetic rats through the exosomal transfer of miR-320 into endothelial cells. Journal of Molecular and Cellular Cardiology 2014;74:139–150. doi: 10.1016/j.yjmcc.2014.05.001.
  19. Wang P, Luo Y, Duan H, et al. MicroRNA 329 Suppresses Angiogenesis by Targeting CD146. Molecular and Cellular Biology 2013;33(18):3689–3699.
    PMid:23878390 PMCid:PMC3753872
  20. Slimani H, Zhai Y, Yousif NG, et al. Enhanced monocyte chemoattractant protein-1 production in aging mice exaggerates cardiac depression during endotoxemia. Critical Care 2014:18:527. https://doi.org/10.1186/s13054-014-0527-8
  21. Ohyagi-Hara C, Sawada K, Kamiura S, et al. MiR-92a inhibits peritoneal dissemination of ovarian cancer cells by inhibiting integrin α5 expression. The American Journal of Pathology 2013;182(5):1876–1889.
  22. Bonauer A, Carmona G, Iwasaki M, et al. MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in Mice. Science 2009;324(5935):1710–1713.
  23. Hinkel R, Penzkofer D, Zühlke S, et al. Inhibition of microRNA-92a protects against ischemia/reperfusion injury in a large-animal model. Circulation 2013;128(10):1066–1075.
  24. Jing Z, Han W, Sui X, Xie J, Pan H. Interaction of autophagy with microRNAs and their potential therapeutic implications in human cancers. Cancer Letters 2015;356(2):332–338.
  25. Bao L, Lv L, Feng J, et al. Mir-487b-5p regulates temozolomide resistance of lung cancer cells through lamp2-medicated autophagy. DNA and Cell Biology 2016;35(8):385–392.
  26. Lim Y, Kumar S. A single cut to pyroptosis. Oncotarget 2015;6(35):36926–36927. https://doi.org/10.18632/oncotarget.6142
    PMid:26485769 PMCid:PMC4741905
  27. Jeyabal P, Thandavarayan RA, Joladarashi D, et al. MicroRNA-9 inhibits hyperglycemia-induced pyroptosis in human ventricular cardiomyocytes by targeting ELAVL1. Biochemical and Biophysical Research Communications 2016;471(4):423–429.
    PMid:26898797 PMCid:PMC4818978
  28. Austin EW, Yousif NG, L Ao L, et al. Ghrelin reduces myocardial injury following global ischemia and reperfusion via suppression of myocardial inflammatory response. American journal of BioMedicine 2013;1(2):38-48.
  29. Carmeliet P. Angiogenesis in life, disease and medicine. Nature 2005;438(7070):932–936.
  30. Yousif NG, Hadi NR, Hassan AM. Indocyanine green-001 (ICG-001) attenuates wnt/β-catenin-induces myocardial injury following sepsis. J Pharmacol Pharmacother 2017;8(1):14-20. doi: 10.4103/jpp.JPP_153_16
  31. Esser JS, Saretzki E, Pankratz F, et al. Bone morphogenetic protein 4 regulates microRNAs miR-494 and miR-126–5p in control of endothelial cell function in angiogenesis. Thrombosis and Haemostasis 2017;117(4):734–749.
  32. Doebele C, Bonauer A, Fischer A, et al. Members of the microRNA-17–92 cluster exhibit a cell-intrinsic antiangiogenic function in endothelial cells. Blood. 2010;115(23):4944–4950.
  33. Dews M, Homayouni A, Yu D, et al. Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster. Nature Genetics 2006;38(9):1060–1065.
    PMid:16878133 PMCid:PMC2669546


1. Access this article through OpenAthens

2. Access this article through your login credentials/Subscription

Get Access

3. Purchase this article at rate $55.00 and received Full-Text/PDF
You will have online immediate access to article following the completion of this purchase and you may download and print a copy of each article for your personal use. Use the coding below to purchase your article as PDF by credit card, debit card, will be asked to supply your billing card information. Before continue with your purchase please read carefully the BM-Publisher terms and conditions of purchase.

Purchase Article

For any technique error please contact us and will be response to sending purchase article by email.

Who Can Become a Reviewer?
Any expert in the article's research field can become a reviewer with American Journal of Biomedicine. Editors might ask you to look at a specific aspect of an article,...

Find out more

Thank you for visiting American Journal of BioMedicine. * = Required fields

Error: Contact form not found.

Case Report

DOI: 10.18081/2333-5106/016-12/543-552
American Journal of BioMedicine Volume 4, Issue 12, pages 543-552
Received July 13, 2016; accepted November 11, 2016; published December 16, 2016
Cited by in Scopus

How to cite this article
Sambol J, Horton J, Chen H, Gonzales C, Faulkner J. MicroRNA-137 protects burn-induced myocardial depression via regulation of the Notch signaling pathway. American Journal of BioMedicine 2016;4(12):543-552.

Article outline
1. Abstract
2. Keywords
3. Introduction
4. Method and Materials
5. Results
6. Discussion
7. Acknowledgements
8. References

Explore PlumX Metrics