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 JBM  Vol.4 No.12 , December 2016
Cell Morphology Modified by Biomaterial Induces miR-21 Expression and Apoptosis
Abstract:
Biochemical factors can play an important role in regulating gene expression in human umbilical vein endothelial cells (HUVECs), yet the role of biophysical factors during this process is unknown. Here, we show that physical cues, in the form of parallel microgrooves on the surface of cell adhesive substrates, can change the morphology of HUVECs as well as specific microRNA expression. Cells cultured on microgrooved poly (dimethyl siloxane) (PDMS) surface exhibited a more elongated morphology relative to those cultured on flat surfaces, and favored outgrowth along the axis of groove alignment. The level of microRNAs in the cell was screened by miRNA microchip and verified by qRT-PCR. The result showed that around 26 microRNAs have been modified significantly, among which miR-21 level was dramatically elevated. Western-blotting analysis demonstrated that PTEN, a target of miR- 21, was up-regulated in HUVECs with elongated morphology. Cell apoptosis level was significantly decreased, with was associated with the increasing of miR-21 level. These results suggested that biophysical factors can directly modify HUVECs morphology, thus induce miR-21 expression in HUVECs and its downstream biological functions such as decreasing apoptosis. This study provided evidence that surface microtopology should also be considered in designing biomaterials in tissue engineering application.
Cite this paper: Liu, M. , Gu, S. and Zhou, Y. (2016) Cell Morphology Modified by Biomaterial Induces miR-21 Expression and Apoptosis. Journal of Biosciences and Medicines, 4, 42-48. doi: 10.4236/jbm.2016.412007.
References

[1]   Akkol, E.K., Süntar, I., Orhan, I.E., et al. (2011) Assessment of Dermal Wound Healing and In Vitro Antioxidant Properties of Avena Sativa L. Journal of Cereal Science, 53, 285-290. http://dx.doi.org/10.1016/j.jcs.2011.01.009

[2]   Maalej, H., Moalla, D., Boisset, C., et al. (2014) Rhelogical, Dermal Wound Healing and In Vitro, Antioxidant Properties of Exopolysaccharide Hydrogel from Pseudomonas stutzeri, AS22. Colloids & Surfaces B Biointerfaces, 123, 814-824. http://dx.doi.org/10.1016/j.colsurfb.2014.10.017

[3]   Khaing, Z.Z., Ehsanipour, A., Hofstetter, C.P., et al. (2016) Injectable Hydrogels for Spinal Cord Repair: A Focus on Swelling and Intraspinal Pressure. Cells Tissues Organs, 202. http://dx.doi.org/10.1159/000446697

[4]   Chien, S. (2007) Mechanotransduction and Endothelial Cell Homeostasis: The Wisdom of the Cell. Ajp Heart & Circulatory Physiology, 292, 135-180.

[5]   Weber, M., Baker, M.B., Moore, J.P., et al. (2010) MiR-21 Is Induced in Endothelial Cells by Shear Stress and Modulates Apoptosis and eNOS Activity. Biochemical & Biophysical Research Communications, 393, 643-648. http://dx.doi.org/10.1016/j.bbrc.2010.02.045

[6]   Downing, T.L., Soto, J., Morez, C., et al. (2013) Biophysical Regulation of Epigenetic State and Cell Reprogramming. Nature Material, 12, 1154-1162. http://dx.doi.org/10.1038/nmat3777

[7]   Fang, Y., Shi, C., Manduchi, E., Civelek, M. and Davies, P.F. (2010) MicroRNA-10a Regulation of Proinflammatory Phenotype in Athero-Susceptible Endothelium in Vivo and in Vitro. Proc. Natl Acad. Sci. USA, 107, 13450-13455. http://dx.doi.org/10.1073/pnas.1002120107

[8]   Fang, Y., Shi, C., Manduchi, E., et al. (2010) MicroRNA-10a Regulation of Proinflammatory Phenotype in Athero-Susceptible Endothelium in Vivo and in Vitro. Proc Natl Acad Sci USA, 107, 13450-13455. http://dx.doi.org/10.1073/pnas.1002120107

[9]   Qin, X., Wang, X., Wang, Y., et al. (2010) MicroRNA-19a Mediates the Suppressive Effect of Laminar Flow on Cyclin D1 Expression in Human Umbilical Vein Endothelial Cells. Proceedings of the National Academy of Sciences of the United States of America, 107, 3240- 3244. http://dx.doi.org/10.1073/pnas.0914882107

[10]   Li, L., Chen, X.P. and Li, Y.J. (2010) MicroRNA-146a and Human Disease. Scand. J. Immunol., 71, 227-231. http://dx.doi.org/10.1111/j.1365-3083.2010.02383.x

[11]   Fichtlscherer, S., De Rosa, S., Fox, H., et al. (2010) Circulating miRNAs in Patients with Coronary Artery Disease. CircRes, 107, 677-684. http://dx.doi.org/10.1161/CIRCRESAHA.109.215566

[12]   Ugalde, A.P., Ramsay, A.J., Rosa, J.D.L., et al. (2011) Aging and Chronic DNA Damage Response Activate a Regulatory Pathway Involving miR-29 and p53. Embo Journal, 30, 2219- 2232. http://dx.doi.org/10.1038/emboj.2011.124

[13]   Martinez, I., Cazalla, D., Almstead, L.L., Steitz, J.A. and DiMaio, D. (2011) miR-29 and miR-30 Regulate B-Myb Expression during Cellular Senescence. Proceedings of the National Academy of Sciences, 108, 522-527. http://dx.doi.org/10.1073/pnas.1017346108

[14]   Chen, K.C., Wang, Y.S., Hu, C.Y., et al. (2011) OxLDL Up-Regulates microRNA-29b, Leading to Epigenetic Modifications of MMP-2/MMP-9 Genes: A Novel Mechanism for Cardiovascular Diseases. Faseb Journal Official Publication of the Federation of American Societies for Experimental Biology, 25, 1718-1728. http://dx.doi.org/10.1096/fj.10-174904

[15]   Zhang, Y., Liu, D., Chen, X., Li, J., Li, L., Bian, Z., et al. (2010) Secreted Monocytic miR-150 Enhances Targeted Endothelial Cell Migration. Mol Cell, 39, 133-144. http://dx.doi.org/10.1016/j.molcel.2010.06.010

[16]   Kurpinski, K. and Li, S. (2006) Anisotropic Mechanosensing by Mesenchymal Stem Cells. Proceedings of the National Academy of Sciences of the United States of America, 103, 16095-16100. http://dx.doi.org/10.1073/pnas.0604182103

[17]   Downing, T.L., Soto, J., Morez, C., et al. (2013) Biophysical Regulation of Epigenetic State and Cell Reprogramming. Nature Material, 12, 1154-1162. http://dx.doi.org/10.1038/nmat3777

[18]   Thakar, R.G., Ho, F., Huang, N.F., et al. (2003) Regulation of Vascular Smooth Muscle Cells by Micropatterning. Biochemical & Biophysical Research Communications, 307, 883-890. http://dx.doi.org/10.1016/S0006-291X(03)01285-3

 
 
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