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EFFECT OF NEGATIVE FEEDBACK LOOP WITH NRF1 AND MIR-378 OF NONALCOHOLIC FATTY LIVER DISEASE: A MATHEMATICAL MODELING APPROACH

  • Lee, SiEun (Department of Mathematics, Pusan National University) ;
  • Shin, Kiyeon (Department of Mathematics, Pusan National University)
  • Received : 2020.03.12
  • Accepted : 2020.04.20
  • Published : 2020.05.31

Abstract

Nonalcoholic fatty liver is a type of fatty liver in which fat accumulates in the liver without alcohol. In the accumulation, Nrf1 and miR-378 genes play very important role, so called negative feedback loop, in which the two genes suppress the other's production. In other words, Nrf1 activates fatty acid oxidation which promotes fat consumption in the liver, while miR-378 deactivates fatty acid oxidation. Thus, both genes regulate nonalcoholic fatty liver. In this paper, the negative feedback loop of Nrf1 and miR-378 are expressed by a system of ordinary differential equations. And, bifurcation simulation shows the change in the amount of each gene with significant parameter range changes. Bifurcation simulation has also used to determine the thresholds for transit between disease and steady state.

Keywords

References

  1. William W. Hager, Applied numerical linear algebra, (1988). p.239
  2. V.Singh, P.K.Dhar, Systems and synthetic biology, Springer, New York, 2015.
  3. Liss, H.H.Kim, B.N.Finck, PPARs and nonalcoholic fatty liver disease. Biochimie, 136(2017), 65-74. https://doi.org/10.1016/j.biochi.2016.11.009
  4. G.Faye, An introduction to bifurcation theory, NeuroMathComp Laboratory, INRIA, Sophia Antipolis, CNRS, ENS Paris, France, 2011.
  5. D.Jordan, P.Smith, Nonlinear ordinary differential equations: an introduction for scientists and engineers, Vol. 10, Oxford University Press, 2007.
  6. B.P.Ingalls, Mathematical modeling in systems biology: an introduction. MIT press, Boston, 2013.
  7. T.Zhang, A negative feedback loop between microRNA-378 and Nrf1 promotes the development of hepatosteatosis in mice treated with a high fat diet, Metabolism, 85(2018), 183-191. https://doi.org/10.1016/j.metabol.2018.03.023
  8. P.P.Becker, MicroRNAs as mediators in the pathogenesis of non-alcoholic fatty liver disease and steatohepatitis, Zeitschrift fur Gastroenterologie, 52(1)(2014), 1-27. https://doi.org/10.1055/s-0033-1362142
  9. V.Singh, P.K.Dhar, Systems and synthetic biology, Springer, New York, 2015.
  10. M.Parola, E.Novo. Nrf1 gene expression in the liver: a single gene linking oxidative stress to NAFLD, NASH and hepatic tumours, J. Hepatology, 43(6)(2005), 1096-1097. https://doi.org/10.1016/j.jhep.2005.09.008
  11. R.Gesztelyi, The Hill equation and the origin of quantitative pharmacology, Arch. H. Exact Sciences, 66(4)(2012), 427-438. https://doi.org/10.1007/s00407-012-0098-5
  12. F.Kanwal, Risk of hepatocellular cancer in patients with non-alcoholic fatty liver disease, Gastroenterology, 155(6)(2018), 1828-1837. https://doi.org/10.1053/j.gastro.2018.08.024
  13. F.Yan, Dynamical behaviors of Rb-E2F pathway including negative feedback loops involving miR449, PloS one, 7(9)(2012), e43908. https://doi.org/10.1371/journal.pone.0043908
  14. Y.Wang, HIC1 and miR-23 27 24 clusters form a double-negative feedback loop in breast cancer, Cell Death and Diff., 24(3)(2017), 421. https://doi.org/10.1038/cdd.2016.136
  15. P.He, K.Qiu, Y.Jia. Modeling of mesenchymal hybrid epithelial state and phenotypic transitions in EMT and MET processes of cancer cells, Sci. Reports, 8(1)(2018), 14323.
  16. T.Zhang, MicroRNA-378 promotes hepatic inflammation and fibrosis via modulation of the NF-${\kappa}B$-$TNF{\alpha}$ pathway, J. Hepatology, 70(1)(2019), 87-96. https://doi.org/10.1016/j.jhep.2018.08.026
  17. S.Cai, P.Zhou, Z.Liu, Functional characteristics of a double negative feedback loop mediated by microRNAs, Cognitive Neurodynamics, 7(5)(2013), 417-429. https://doi.org/10.1007/s11571-012-9236-7
  18. Gilbert, Scott F. Developmental Biology, Sunderland, MA.(2000), 775-777.