Advertisement

Effect of Long-Term Exercise Training on lncRNAs Expression in the Vascular Injury of Insulin Resistance

  • Suixin Liu
  • Fan Zheng
  • Ying Cai
  • Wenliang Zhang
  • Yaoshan Dun
Original Article
  • 18 Downloads

Abstract

LncRNA microarray analysis was applied to investigate the exercise effect on the global differential expressions of lncRNA and mRNA in aorta endothelium in insulin resistance. Twenty-four male C57BL/6 J mice were randomly divided into three groups: control group (n = 8), high-fat diet group (n = 8), and high-fat diet plus exercise training group (n = 8). An lncRNA microarray analysis was applied to investigate the global differential expressions of lncRNA and mRNA in aorta endothelium among three groups and the results were further verified by qPCR. Hypergeometric distribution analysis was applied to reveal the possible signaling. Exercise might alleviate the vascular injury of IR via FR030200-Col3A1, FR402720-Rnd1, and FR030200/FR402720-Rnd3 signalings in cytoskeletal rearrangement pathway; E2F1-FR030200/FR402720-Nnat and FR030200/ FR402720-Fam46a signalings in anti-inflammation pathway. This study identified a panel of dysregulated lncRNAs and mRNAs that might serve as potential biomarkers relevant to the vascular injury in insulin resistance induced by high-fat diet.

Keywords

lncRNA Insulin resistance Vascular injury Exercise 

Notes

Funding

This project was funded by the National Science Foundation for Young Scientists of China (grant number 81501955).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All institutional and national guidelines for the care and use of laboratory animals were followed and approved by the Central South University Institute Animal Care and Use Committee.

References

  1. 1.
    The Geriatrics Branch of Chinese Medical Association, Editorial Board of Chinese Journal of Internal Med, Editorial Board of Chinese Journal of Geriatrics. (2016). Aspirin use in patients with atherosclerotic cardiovascular disease: the 2016 Chinese expert consensus statement. Chinese Journal Geriatrics, 1, 106–118.Google Scholar
  2. 2.
    Volgman, A. S., Palaniappan, L. S., Aggarwal, N. T., et al. (2018). American Heart Association Council on Epidemiology and Prevention; Cardiovascular Disease and Stroke in Women and Special Populations Committee of the Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; Council on Quality of Care and Outcomes Research; and Stroke Council. Atherosclerotic cardiovascular disease in South Asians in the United States: epidemiology, risk factors, and treatments: a scientific statement from the American Heart Association. Circulation, 138(1), e1–e34.CrossRefGoogle Scholar
  3. 3.
    Hanley, A. J., Williams, K., Stern, M. P., et al. (2002). Homeostasis model assessment of insulin resistance in relation to the incidence of cardiovascular disease: the San Antonio Heart Study. Diabetes Care, 25(7), 1177–1184.CrossRefGoogle Scholar
  4. 4.
    Rutter, M. K., Wilson, P. W., Sullivan, L. M., et al. (2008). Use of alternative thresholds defining insulin resistance to predict incident type 2 diabetes mellitus and cardiovascular disease. Circulation, 117(8), 1003–1009.CrossRefPubMedGoogle Scholar
  5. 5.
    Janus, A., Szahidewiczkrupska, E., Mazur, G., et al. (2016). Insulin resistance and endothelial dysfunction constitute a common therapeutic target in cardiometabolic disorders. Mediators of Inflammation, 2016(1), 1–10.CrossRefGoogle Scholar
  6. 6.
    Patel, T. P., Rawal, K., Bagchi, A. K., et al. (2015). Insulin resistance: an additional risk factor in the pathogenesis of cardiovascular disease in type 2 diabetes. Heart Failure Reviews, 21(1), 11–23.CrossRefGoogle Scholar
  7. 7.
    Kraegen, E. W., Storlien, L. H., Jenkins, A. B., et al. (1989). Chronic exercise compensates for insulin resistance induced by a high-fat diet in rats. The American Journal of Physiology, 256(1), 242–249.Google Scholar
  8. 8.
    Rao, X., Zhong, J., Xu, X., et al. (2013). Exercise protects against diet-induced insulin resistance through downregulation of protein kinase cβ in mice. PLoS One, 8(12), e81364.CrossRefPubMedGoogle Scholar
  9. 9.
    Park, D. R., Park, K. H., Kim, B. J., et al. (2015). Exercise ameliorates insulin resistance via Ca2+ signals distinct from those of insulin for GLUT4 translocation in skeletal muscles. Diabetes, 64(4), 1224.CrossRefGoogle Scholar
  10. 10.
    Ying, C., Suixin, L., Kangling, X., et al. (2014). MicroRNA-492 reverses high glucose-induced insulin resistance in HUVsEC cells through targeting resistin. Molecular and Cellular Biochemistry, 391(2), 117–125.CrossRefPubMedGoogle Scholar
  11. 11.
    Dekang, L., Xiang, W., Jun, D., et al. (2016). Systematic characterization of lncRNAs’ cell-to-cell expression heterogeneity in glioblastoma cells. Oncotarget, 7(14), 18403–18414.Google Scholar
  12. 12.
    Bao, M. H., Luo, H. Q., Chen, L. H., et al. (2016). Impact of high fat diet on long non-coding RNAs and messenger RNAs expression in the aortas of ApoE(−/−) mice. Scientific Reports, 634161.Google Scholar
  13. 13.
    Lin, Z., Li, X., Zhan, X., et al. (2017). Construction of competitive endogenous RNA network reveals regulatory role of long non-coding RNAs in type 2 diabetes mellitus. Journal of Cellular and Molecular Medicine, 21(12), 3204–3213.CrossRefPubMedGoogle Scholar
  14. 14.
    Jia, S., Yuting, R., Ming, W., et al. (2016). Differentially expressed circulating LncRNAs and mRNA identified by microarray analysis in obese patients. Scientific Reports, 635421.Google Scholar
  15. 15.
    Zhang, J., Zhang, N., Liu, M., et al. (2012). Disruption of growth factor receptor–binding protein 10 in the pancreas enhances β-cell proliferation and protects mice from Streptozotocin-induced β-cell apoptosis. Diabetes, 61(12), 3189.CrossRefPubMedGoogle Scholar
  16. 16.
    Arimatsu, K., Yamada, H., Miyazawa, H., et al. (2014). Oral pathobiont induces systemic inflammation and metabolic changes associated with alteration of gut microbiota. Scientific Reports, 4(18), 4828.PubMedCentralPubMedGoogle Scholar
  17. 17.
    Livak, K. J., & Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C (T)) method. Methods, 25(4), 402–408.CrossRefGoogle Scholar
  18. 18.
    Zebda, N., Dubrovskyi, O., & Birukov, K. G. (2012). Focal adhesion kinase regulation of mechanotransduction and its impact on endothelial cell functions. Microvascular Research, 83(1), 71–81.CrossRefPubMedGoogle Scholar
  19. 19.
    Severs, N. J., Rothery, S., Dupont, E., et al. (2015). Immunocytochemical analysis of connexin expression in the healthy and diseased cardiovascular system. Microscopy Research and Technique, 52(3), 301–322.CrossRefGoogle Scholar
  20. 20.
    Ohanian, J., Pieri, M., & Ohanian, V. (2015). Non-receptor tyrosine kinases and the actin cytoskeleton in contractile vascular smooth muscle. Journal of Physiology, 593(17), 3807.CrossRefGoogle Scholar
  21. 21.
    Undas, A., Stepień, E., Branicka, A., et al. (2009). Thrombin formation and platelet activation at the site of vascular injury in patients with coronary artery disease treated with clopidogrel combined with aspirin. Kardiologia Polska, 67(6), 591–598.Google Scholar
  22. 22.
    van Meeteren, L. A., Goumans, M. J., & Ten, D. P. (2011). TGF-β receptor signaling pathways in angiogenesis; emerging targets for anti-angiogenesis therapy. Current Pharmaceutical Biotechnology, 12(12), 2108–2120.CrossRefGoogle Scholar
  23. 23.
    Schad, J. F., Meltzer, K. R., Hicks, M. R., et al. (2011). Cyclic strain upregulates VEGF and attenuates proliferation of vascular smooth muscle cells. Vasc Cell, 3(1), 21.CrossRefPubMedGoogle Scholar
  24. 24.
    Oliver, C. J., Terrylorenzo, R. T., Elliott, E., et al. (2002). Targeting protein phosphatase 1 (PP1) to the actin cytoskeleton: the neurabin I/PP1 complex regulates cell morphology. Molecular & Cellular Biology, 22(13), 4690–4701.CrossRefGoogle Scholar
  25. 25.
    Meyer, M. C., Rastogi, P., Beckett, C. S., et al. (2005). Phospholipase A2 inhibitors as potential anti-inflammatory agents. Current Pharmaceutical Design, 11(10), 1301–1312.CrossRefGoogle Scholar
  26. 26.
    Martínezgarcía, C., Izquierdolahuerta, A., Vivas, Y., et al. (2015). Renal lipotoxicity-associated inflammation and insulin resistance affects actin cytoskeleton organization in podocytes. PLoS One, 10(11), e0142291.CrossRefGoogle Scholar
  27. 27.
    Bharti, B., & Dey, C. S. (2008). Focal adhesion kinase contributes to insulin-induced actin reorganization into a mesh harboring glucose transporter-4 in insulin resistant skeletal muscle cells. BMC Cell Biology, 9(1), 1–12.CrossRefGoogle Scholar
  28. 28.
    Mccullagh, K. A., & Balian, G. (1975). Collagen characterisation and cell transformation in human atherosclerosis. Nature, 258(5530), 73–75.CrossRefGoogle Scholar
  29. 29.
    Faugeroux, J., Nematalla, H., Li, W., et al. (2013). Angiotensin II promotes thoracic aortic dissections and ruptures in Col3a1 haploinsufficient mice. Hypertension, 62(1), 203–208.CrossRefGoogle Scholar
  30. 30.
    Oinuma, I., Kawada, K., Tsukagoshi, K., et al. (2012). Rnd1 and Rnd3 targeting to lipid raft is required for p190 RhoGAP activation. Molecular Biology of the Cell, 23, 1593.CrossRefPubMedGoogle Scholar
  31. 31.
    Loirand, G., Cario-Toumaniantz, C., Chardin, P., et al. (1999). The rho-related protein Rnd1 inhibits Ca2+ sensitization of rat smooth muscle. The Journal of Physiology, 516(3), 825–834.CrossRefPubMedGoogle Scholar
  32. 32.
    Chun, K. H., Araki, K., Jee, Y., et al. (2012). Regulation of glucose transport by ROCK1 differs from that of ROCK2 and is controlled by actin polymerization. Endocrinology, 153(4), 1649–1662.CrossRefPubMedGoogle Scholar
  33. 33.
    Chen, M., Capps, C., Willerson, J. T., et al. (2002). E2F-1 regulates nuclear factor-kappaB activity and cell adhesion: potential antiinflammatory activity of the transcription factor E2F-1. Circulation, 106(21), 2707–2713.CrossRefPubMedGoogle Scholar
  34. 34.
    Mzhavia, N., Yu, S., Ikeda, S., et al. (2008). Neuronatin: a new inflammation gene expressed on the aortic endothelium of diabetic mice. Diabetes, 57(10), 2774–2784.CrossRefPubMedGoogle Scholar
  35. 35.
    Gburcik, V., Cleasby, M. E., & Timmons, J. A. (2013). Loss of neuronatin promotes “browning” of primary mouse adipocytes while reducing Glut1-mediated glucose disposal. American Journal of Physiology. Endocrinology and Metabolism, 304(8), E885–E894.CrossRefPubMedGoogle Scholar
  36. 36.
    Carayol, J., Chabert, C., Cara, A. D., et al. (2017). Protein quantitative trait locus study in obesity during weight-loss identifies a leptin regulator. Nature Communications, 8(1), 2084.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Suixin Liu
    • 1
  • Fan Zheng
    • 1
  • Ying Cai
    • 1
  • Wenliang Zhang
    • 1
  • Yaoshan Dun
    • 1
  1. 1.Cardiac Rehabilitation Center of Rehabilitation Department, Xiangya HospitalCentral South UniversityChangshaPeople’s Republic of China

Personalised recommendations