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Fluid shear stress induces endothelial KLF2 gene expression through a defined promoter region

  • Justin P. Huddleson , Seetha Srinivasan , Nisar Ahmad and Jerry B. Lingrel
Published/Copyright: June 1, 2005
Biological Chemistry
From the journal Volume 385 Issue 8

Abstract

Fluid shear stress is crucial for maintenance of a properly functioning endothelium. In this study we demonstrate that the KLF2 transcription factor is greatly induced by pulsatile shear stress in murine microvascular endothelial cells. The promoter elements responsible for the induction were studied by transfection with luciferase-reporter plasmids including the 5′ flanking region of the murine KLF2 gene. Deletion analysis reveals that the responses are regulated by a region from -157 to -95 bp from the start site of transcription. Furthermore, shear stress induces specific nuclear binding within this region. These results define a novel shear stress response region that is highly conserved between mouse and human homologs.

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References

Anderson, K.P., Kern C.B., Crable, S.C., and Lingrel, J.B. (1995). Isolation of a gene encoding a functional zinc funger protein homologous to erythroid Krüppel-like factor: identification of a new multigene family. Mol. Cell. Biol.15, 5957–5965.10.1128/MCB.15.11.5957Search in Google Scholar

Ballermann, B.J., Dardik, A., Eng, E., and Liu, A. (1998). Shear stress and the endothelium. Kidney Int.54, S100–S108.10.1046/j.1523-1755.1998.06720.xSearch in Google Scholar

Banerjee, S.S., Feinberg, MW., Watanabe, W., Gray, S., Haspel, R.L., Denkinger, D.J.,. Kawahara, R., Hauner, H., and Jain, M.K. (2003). The Krüppel-like factor KLF2 inhibits peroxisome proliferator-activated receptor-γ expression and adipogenesis. J. Biol. Chem.278, 2581–2584.10.1074/jbc.M210859200Search in Google Scholar

Benjamin, L.E. (2000). The controls of microvascular survival. Cancer Metastasis Rev.19, 75–81.10.1023/A:1026552415576Search in Google Scholar

Bird, A.P. (1986). CpG-rich islands and the function of DNA methylation. Nature321, 209–213.10.1038/321209a0Search in Google Scholar

Buckley, A.F., Kuo, C.T., and Leiden, J.M. (2001). Transcription factor LKLF is sufficient to program T cell quiescence via a c-Myc-dependent pathway. Nature Immunol.2, 698–704.10.1038/90633Search in Google Scholar

Chen, B.P.C., Li, Y-S., Zhao, Y., Chen, K-D., Li, S., Lao, J., Yuan, S., Shyy, J.Y-J., and Chien, S. (2001). DNA microarray analysis of gene expression in endothelial cells in response to 24-h shear stress. Physiol. Genomics7, 55–63.10.1152/physiolgenomics.2001.7.1.55Search in Google Scholar

Dekker, R.J., van Soest, S., Fontijn, R.D., Salamanca, S., de Groot, P.G., VanBavel, E., Pannekoek, H., and Horrevoets, A.J.G. (2002). Prolonged fluid shear stress induces a distinct set of endothelial genes, most specifically lung kruppel-like factor (KLF2). Blood100, 1689–1698.10.1182/blood-2002-01-0046Search in Google Scholar

Dimmeler, S., Haendeler, J., Rippmann, V., Nehls, M., and Zeiher, A.M. (1996). Shear stress inhibits apoptosis of human endothelial cells. FEBS Lett.399, 71–74.10.1016/S0014-5793(96)01289-6Search in Google Scholar

Egashira, K. (2002). Clinical importance of endothelial function in arteriosclerosis and ischemic heart disease. Circ. J.66, 529–533.10.1253/circj.66.529Search in Google Scholar PubMed

Freyberg, M.A., Kaiser, D., Graf, R., Buttenbender, J., and Friedl, P. (2001). Proatherogenic flow conditions initiate endothelial apoptosis via thrombospondin-1 and the integrin-associated protein. Biochem. Biophys. Res. Commun.286, 141–149.10.1006/bbrc.2001.5314Search in Google Scholar

Friedman, M.H., O’Brien, V., and Ehrlich, L.W. (1975). Calculations of pulsatile flow through a branch: implications for the hemodynamics of atherogenesis. Circ. Res.36, 277–285.10.1161/01.RES.36.2.277Search in Google Scholar

Groenendijk, B.C.W., Hierck, B.P., Gittenberger-de Groot, A.C., and Poelmann, R.E. (2004). Development-related changes in expression of shear stress responsive genes KLF-2, ET-1, and NOS-3 in the developing cardiovascular system of chicken embryos. Dev. Dynamics230, 576–68.Search in Google Scholar

Jegga, A.G., Sherwood, S.P., Carman, J.W., Pinski, A.T., Phillips, J.L., Pestian, J.P. and Aronow, B.J. (2002). Detection and visualization of compositionally similar cis-regulatory element clusters in orthologous and coordiantely controlled genes. Genome Res.12, 1408–1417.10.1101/gr.255002Search in Google Scholar

Kadonaga, J.T., Carner, K.R., Masiarz, F.R., and Tjian, R. (1987). Isolation of cDNA transcription factor Sp1 and functional analysis of the DNA binding domain. Cell51, 1079–1090.10.1016/0092-8674(87)90594-0Search in Google Scholar

Khachigian, L.M., Anderson, K.R., Halnon, N.J., Gimbrone, M.A., Jr., Resnick, N., and Collins, T. (1997). Egr-1 is activated in endothelial cells exposed to fluid shear stress and interacts with a novel shear-stress-response element in the PDGF A-chain promoter. Arterioscler. Thromb. Vasc. Biol.17, 2280–2286.10.1161/01.ATV.17.10.2280Search in Google Scholar

Kozyrev, S.V., Hansen, L.L., Poltaraus, A.B., Domninsky, D.A., and Kisselev, L.L. (1999). Structure of the human CpG-island containing lung Kruppel-like factor (LKLF) gene and its location in chromosome 19p13.11-13 locus. FEBS Lett.448, 149–152.10.1016/S0014-5793(99)00348-8Search in Google Scholar

Kuo, C.T., Veselits, M.L., Barton, K.P., Lu, M.M., Clendenin, C., and Leiden, J.M. (1997a). The LKLF transcription factor is required for normal tunica media formation and blood vessel stabilization during murine embryogenesis. Genes Dev.11, 2996–3006.10.1101/gad.11.22.2996Search in Google Scholar

Kuo, C.T., Veselits, M.L., and Leiden, J.M. (1997b). KLF2: a transcriptional regulator of single-positive T cell quiescence and survival. Science277, 1986–1990.10.1126/science.277.5334.1986Search in Google Scholar

Lan, Q., Mercurius, K.O., and Davies, P.F. (1994). Stimulation of transcription factors NF-κB and AP1 in endothelial cells subjected to shear stress. Biochem. Biophys. Res. Commun.201, 950–956.10.1006/bbrc.1994.1794Search in Google Scholar

Lehoux, S., and Tedgui, A. (2003). Cellular mechanics and gene expression in blood vessels. J. Biomech.36, 631–643.10.1016/S0021-9290(02)00441-4Search in Google Scholar

Lin, K., Hsu, P-P., Chen, B.P., Yuan, S., Usami, S., Shyy, J.Y-J., Li, Y-S., and Chien, S. (2000). Molecular mechanisms of endothelial growth arrest by laminar shear stress. Proc. Natl. Acad. Sci. USA97, 9385–9389.10.1073/pnas.170282597Search in Google Scholar

Lin, Y., Ryan, J., Lewis, J., Wani, M.A., Lingrel, J.B., and Liu, Z. (2003). TRAF2 exerts its antiapoptotic effect by regulating the expression of Kruppel-like factor LKLF. Mol. Cell. Biol.23, 5849–5856.10.1128/MCB.23.16.5849-5856.2003Search in Google Scholar

Lipowsky, H.H. (1995). Shear stress in circulation. In: Flow-Dependent Regulation of Vascular Function. Clinical Physiology Series, American Physiological Society, J.A. Bevan, G.K. Kaley and G. Rubanyi, eds. (New York, USA: Oxford University Press), pp. 28–45.10.1007/978-1-4614-7527-9_2Search in Google Scholar

Malek, A.M. and Izumo, S. (1995). Control of endothelial cell gene expression by flow. J. Biomech.28, 1515–1528.10.1016/0021-9290(95)00099-2Search in Google Scholar

Obeso, J., Weber, J., and Auerbach, R. (1990). A hemangioendothelioma-derived cell line: its use as a model for the study of endothelial cell biology. Lab. Invest.63, 259–269.Search in Google Scholar

Pfaffl, M.W. (2001). A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res.29, 2003–2007.10.1093/nar/29.9.e45Search in Google Scholar

Redmond, E.M., Cahill, P.A., and Sitzman, J.V. (1995). Perfused transcapillary smooth muscle and endothelial cell co-culture – a novel in vitro model. In Vitro Cell. Dev. Biol.31, 601–609.10.1007/BF02634313Search in Google Scholar

Resnick, N., Collins, T., Atkinson, W., Bonthron, D.T., Dewey Jr., C.F., and Gimbrone Jr., M.A. (1993). Platelet-derived growth factor B chain promoter contains a cis-acting fluid shear stress-responsive element. Proc. Natl. Acad. Sci. USA90, 4591–4595.10.1073/pnas.90.10.4591Search in Google Scholar

Resnick, N. and Gimbrone, M.A., Jr. (1995). Hemodynamic forces are complex regulators of endothelial gene expression. FASEB J.9, 874–882.10.1096/fasebj.9.10.7615157Search in Google Scholar

Resnick, N., Yahav, H., Shay-Salit, A., Shushy, M., Schubert, S., Zilberman, L.C.M., and Wofowitz, E. (2003). Fluid shear stress and the vascular endothelium: for better or worse. Life Sci.81, 177–199.10.1016/S0079-6107(02)00052-4Search in Google Scholar

Ross, R. (1999). Atherosclerosis-an inflammatory disease. N. Engl. J. Med.340, 115–126.10.1056/NEJM199901143400207Search in Google Scholar PubMed

Schrick, J.J., Hughes, M.J., Anderson, K.P., Croyle, M.L., and Lingrel, J.B. (1999). Characterization of the lung Kruppel-like transcription factor gene and upstream regulatory elements. Gene236, 185–195.10.1016/S0378-1119(99)00235-8Search in Google Scholar

SenBanerjee, S., Lin, Z., Atkins, G.B., Greif, D.M., Rao, R.M., Kumar, A., Feinberg, M.W., Chen, Z., Simon, D.I., Luscinskas, F.W. et al. (2004). KLF2 is a novel transcriptional regulator of endothelial proinflammatory activation. J. Exp. Med.199, 1305–1315.10.1084/jem.20031132Search in Google Scholar

Skalak, T.C., and Price, R.J. (1996). The role of mechanical stresses in microvascular remodeling. Microcirculation3, 143–165.10.3109/10739689609148284Search in Google Scholar

Thiel, G. and Cibelli, G. (2002). Regulation of life and death by the zinc finger transcription factor Egr-1. J. Cell Physiol.193, 287–292.10.1002/jcp.10178Search in Google Scholar

Traub, O. and Berk, B.C. (1998). Laminar shear stress: mechanisms by which endothelial cells transducer an atheroprotective force. Arterioscler. Thromb. Vasc. Biol.18, 677–685.10.1161/01.ATV.18.5.677Search in Google Scholar

Urbich, C., Stein, M., Reisinger, K., Kaufmann, R., Dimmeler, S., and Gille, J. (2003). Fluid shear stressd-induced transcriptional activation of vascular endothelial growth factor receptor-2 gene requires Sp1-dependent DNA binding. FEBS Lett.535, 87–93.10.1016/S0014-5793(02)03879-6Search in Google Scholar

Wani, M.A., Means Jr., R.T. and Lingrel, J.B. (1998). Loss of LKLF function results in embryonic lethality in mice. Transgenic Res.7, 229–238.10.1023/A:1008809809843Search in Google Scholar

Wani, M.A., Wert, S.E., and Lingrel, J.B. (1999). Lung Kruppellike factor, a zinc finger transcription factor, is essential for normal lung development. J. Biol. Chem.274, 21180–21185.10.1074/jbc.274.30.21180Search in Google Scholar PubMed

Wasserman, S.M., Mehraban, F., Komuves, L.G., Yang, R-B., Tomlinson, J.E., Zhang, Y., Spriggs, F., and Topper, J.N. (2002). Gene expression profile of human endothelial cells exposed to sustained fluid shear stress. Physiol. Genomics12, 13–23.10.1152/physiolgenomics.00102.2002Search in Google Scholar PubMed

Watt, F. and Molloy, P.L. (1988). Cytosine methylation preventsbinding to DNA of a HeLa cell transcription factor requiredfor optimal expression of the adenovirus major late promoter. Genes Dev.2, 1136–1143.10.1101/gad.2.9.1136Search in Google Scholar PubMed

Published Online: 2005-06-01
Published in Print: 2004-08-01

© Walter de Gruyter

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