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Inhibitory Smad transcription factors protect arterial endothelial cells from apoptosis induced by BMP4

Oncogene volume 25, pages 7131–7137 (2006)Cite this article

Abstract

Arterial endothelial cells (EC) at the adult stage differ from capillary and venous EC in terms of resistance to stress; however, the molecular basis of this resistance is not clear. Here, we found that arterial EC are highly resistant to bone morphogenetic protein (BMP)4-dependent apoptosis, whereas capillary and venous EC are not. The expression of inhibitory Smads (I-Smads) in arterial EC was well correlated with the resistance to this apoptosis. After the knockdown of I-Smad expression by short interfering RNA, the resistant arterial EC became sensitive to BMP4. In contrast, the ectopic expression of I-Smads in BMP4-sensitive cells suppressed BMP4-induced apoptosis. Furthermore, intravenous administration of BMP4 into mice caused hemorrhage of capillary EC in brain and lung. These results strongly suggest that BMP4/I-Smads are a novel regulator for the stability of vascular EC.

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References

  • Bourdeau A, Faughnan ME, Letarte M . (2000). Trends Cardiovasc Med 10: 279–285.

  • Duff SE, Li C, Garland JM, Kumar S . (2003). FASEB J 17: 984–992.

  • Graham A, Francis-West P, Brickell P, Lumsden A . (1994). Nature 372: 684–686.

  • Gu K, Smoke RH, Rutherford RB . (1996). Arch Oral Biol 41: 919–923.

  • Hanyu A, Ishidou Y, Ebisawa T, Shimanuki T, Imamura T, Miyazono K . (2001). J Cell Biol 155: 1017–1027.

  • Hata A, Lagna G, Massague J, Hemmati-Brivanlou A . (1998). Genes Dev 12: 186–197.

  • Herzog Y, Kalcheim C, Kahane N, Reshef R, Neufeld G . (2001). Mech Dev 109: 115–119.

  • Imamura T, Takase M, Nishihara A, Oeda E, Hanai J, Kawabata M et al. (1997). Nature 389: 622–626.

  • Ishisaki A, Yamato K, Hashimoto S, Nakao A, Tamaki K, Nonaka K et al. (1999). J Biol Chem 274: 13637–13642.

  • Kimura N, Matsuo R, Shibuya H, Nakashima K, Taga T . (2000). J Biol Chem 275: 17647–17652.

  • Kiyono M, Shibuya M . (2003). Mol Cell Biol 23: 4627–4636.

  • le Noble F, Moyon D, Pardanaud L, Yuan L, Djonov V, Matthijsen R et al. (2004). Development 131: 361–375.

  • Massague J . (1998). Annu Rev Biochem 67: 753–791.

  • Moyon D, Pardanaud L, Yuan L, Breant C, Eichmann A . (2001). Development 128: 3359–3370.

  • Nakao A, Afrakhte M, Moren A, Nakayama T, Christian JL, Heuchel R et al. (1997). Nature 389: 631–635.

  • Patan S . (2004). Cancer Treat Res 117: 3–32.

  • Shawber CJ, Das I, Francisco E, Kitajewski J . (2003). Ann NY Acad Sci 995: 162–170.

  • Shibuya M . (2001). Cell Struct Funct 26: 25–35.

  • Shibuya M, Ito N, Claesson-Welsh L . (1999). Curr Top Microbiol Immunol 237: 59–83.

  • Shin D, Garcia-Cardena G, Hayashi S, Gerety S, Asahara T, Stavrakis G et al. (2001). Dev Biol 230: 139–150.

  • Souchelnytskyi S, Nakayama T, Nakao A, Moren A, Heldin CH, Christian JL et al. (1998). J Biol Chem 273: 25364–25370.

  • Topper JN, Cai J, Qiu Y, Anderson KR, Xu YY, Deeds JD et al. (1997). Proc Natl Acad Sci USA 94: 9314–9319.

  • Wang HU, Chen ZF, Anderson DJ . (1998). Cell 93: 741–753.

  • Yancopoulos GD, Klagsbrun M, Folkman J . (1998). Cell 93: 661–664.

  • Zou H, Niswander L . (1996). Science 272: 738–741.

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Acknowledgements

We thank Dr K Miyazono for kindly providing us with plasmids pcDNA3-FLAG-Smad6 and pcDNA3-FLAG-Smad7. This work was supported by Grants-in-Aid for Special Project Research on Cancer-Bioscience (12215024, 17014020) from the Ministry of Education, Science, Sports and Culture of Japan and for the program ‘Research for the Future’ of the Japan Society for the Promotion of Science and the program ‘Promotion of Fundamental Research in Health Sciences’ from the Organization for Pharmaceutical Safety and Research (OPSR).

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  1. Department of Genetics, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan

    M Kiyono & M Shibuya

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  1. M Kiyono
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Correspondence to M Shibuya.

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Kiyono, M., Shibuya, M. Inhibitory Smad transcription factors protect arterial endothelial cells from apoptosis induced by BMP4. Oncogene 25, 7131–7137 (2006). https://doi.org/10.1038/sj.onc.1209700

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