Abstract
The increasing wall stress as is elicited by arterial hypertension promotes their reorganization in the vessel wall which may lead to arterial stiffening and contractile dysfunction. The nuclear factor of activated T cells 5 (NFAT5) pathway plays a role in regulating growth and differentiation in various cell types. We investigated whether the NFAT5 pathway was involved in the regulation of biomechanical stretch-induced human arterial smooth muscle cell (HUASMC) proliferation, inflammation, and migration. Herein, we showed that stretch promoted the expression of NFAT5 in human arterial smooth muscle cells and regulated through activation of c-Jun N-terminal kinase under these conditions. This may contribute to an improved activity of HUASMCs and thus promote reorganization in vascular remodeling processes such as hypertension-induced arterial stiffening and contractile dysfunction.
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28 July 2020
After the publication of our article, we became aware that there were errors in Fig.��3c and 3d were incorrectly presented.
References
Olivetti, G., M. Melissari, G. Marchetti, and P. Anversa. 1982. Quantitative structural changes of the rat thoracic aorta in early spontaneous hypertension. Tissue composition, and hypertrophy and hyperplasia of smooth muscle cells. Circulation Research 51 (1): 19–26.
Feldner, A., H. Otto, S. Rewerk, M. Hecker, and T. Korff. 2011. Experimental hypertension triggers varicosis-like maladaptive venous remodeling through activator protein-1. The FASEB Journal 25 (10): 3613–3621.
Pfisterer, L., A. Feldner, M. Hecker, and T. Korff. 2012. Hypertension impairs myocardin function: a novel mechanism facilitating arterial remodelling. Cardiovascular Research 96 (1): 120–129.
Nordström, I., K. Dreja, U. Malmqvist, and P. Hellstrand. 2000. Stretch-dependent modulation of contractility and growth in smooth muscle of rat portal vein. Circulation Research 87 (3): 228–234.
Lee, Samuel, and Richard T. Lee. 2010. Mechanical stretch and intimal hyperplasia: the missing link?[J]. Arteriosclerosis Thrombosis & Vascular Biology 30 (3): 459–460.
Li, S., D.Z. Wang, Z. Wang, J.A. Richardson, and E.N. Olson. 2003. The serum response factor coactivator myocardin is required for vascular smooth muscle development. Proceedings of the National Academy of Sciences 100 (16): 9366–9370.
Halterman, J.A., H.M. Kwon, and B.R. Wamhoff. 2012. Tonicity-independent regulation of the osmosensitive transcription factor TonEBP (NFAT5). American Journal of Physiology-Cell Physiology 302 (1): C1–C8.
Ho, S.N. 2003. The role of NFAT5/TonEBP in establishing an optimal intracellular environment. Archives of Biochemistry and Biophysics 413 (2): 151–157.
Woo, S., S. Lee, and M.H. Kwon. 2002. TonEBP transcriptional activator in the cellular response to increased osmolality. Pflügers Archiv European Journal of Physiology 444 (5): 579–585.
Jauliac, S., C. López-Rodriguez, L.M. Shaw, L.F. Brown, A. Rao, and A. Toker. 2002. The role of NFAT transcription factors in integrin-mediated carcinoma invasion. Nature Cell Biology 4 (7): 540–544.
O'Connor, R.S., S.T. Mills, K.A. Jones, S.N. Ho, and G.K. Pavlath. 2007. A combinatorial role for NFAT5 in both myoblast migration and differentiation during skeletal muscle myogenesis. Journal of Cell Science 120 (1): 149–159.
Go, W.Y., X. Liu, M.A. Roti, F. Liu, and S.N. Ho. 2004. NFAT5/TonEBP mutant mice define osmotic stress as a critical feature of the lymphoid microenvironment. Proceedings of the National Academy of Sciences of the United States of America 101 (29): 10673–10678.
Halterman, J.A., H.M. Kwon, R. Zargham, P.D. Bortz, and B.R. Wamhoff. 2011. Nuclear factor of activated T cells 5 regulates vascular smooth muscle cell phenotypic modulation. Arteriosclerosis, Thrombosis, and Vascular Biology 31 (10): 2287–2296.
Yoon, H.J., S. You, S.A. Yoo, N.H. Kim, H.M. Kwon, C.H. Yoon, C.S. Cho, D. Hwang, and W.U. Kim. 2011. NF-AT5 is a critical regulator of inflammatory arthritis. Arthritis & Rheumatology 63 (7): 1843–1852.
Machnik, A., W. Neuhofer, J. Jantsch, A. Dahlmann, T. Tammela, K. Machura, J.K. Park, F.X. Beck, D.N. Müller, W. Derer, and J. Goss. 2009. Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C-dependent buffering mechanism. Nature Medicine 15 (5): 545–552.
Roth, I., V. Leroy, H.M. Kwon, P.Y. Martin, E. Féraille, and U. Hasler. 2010. Osmoprotective transcription factor NFAT5/TonEBP modulates nuclear factor-κB activity. Molecular Biology of the Cell 21 (19): 3459–3474.
Buxadé, M., G. Lunazzi, J. Minguillón, S. Iborra, R. Berga-Bolaños, M. del Val, J. Aramburu, and C. López-Rodríguez. 2012. Gene expression induced by Toll-like receptors in macrophages requires the transcription factor NFAT5. Journal of Experimental Medicine 209 (2): 379–393.
Haudenschild, C.C., J.O. Grunwald, and A.V. Chobanian. 1985. Effects of hypertension on migration and proliferation of smooth muscle in culture. Hypertension 7 (3 Pt 2): I101.
Intengan, H.D., and E.L. Schiffrin. 2000. Structure and mechanical properties of resistance arteries in hypertension. Hypertension 36 (3): 312–318.
Brady, P.S., E.A. Park, J.S. Liu, R.W. Hanson, and L.J. Brady. 1992. Isolation and characterization of the promoter for the gene coding for the 68 kDa carnitine palmitoyltransferase from the rat. Biochemical Journal 286 (3): 779–783.
Wang, Z., D.Z. Wang, D. Hockemeyer, J. McAnally, A. Nordheim, and E.N. Olson. 2004. Myocardin and ternary complex factors compete for SRF to control smooth muscle gene expression. Nature 428 (6979): 185–189.
Chen, J., C.M. Kitchen, J.W. Streb, and J.M. Miano. 2002. Myocardin: a component of a molecular switch for smooth muscle differentiation. Journal of Molecular and Cellular Cardiology 34 (10): 1345–1356.
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This research project was supported by the National Natural Science Foundation of China Grant No. 81400294.
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Cao, W., Zhang, D., Li, Q. et al. Biomechanical Stretch Induces Inflammation, Proliferation, and Migration by Activating NFAT5 in Arterial Smooth Muscle Cells. Inflammation 40, 2129–2136 (2017). https://doi.org/10.1007/s10753-017-0653-y
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DOI: https://doi.org/10.1007/s10753-017-0653-y