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Ultrasound up-regulates expression of heme oxygenase-1 gene in endothelial cells

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Abstract

Purpose

We found heme oxygenase-1 (HO-1) gene up-regulation in response to ultrasound stimulation in endothelial cells. This project was started to explore the mechanism since it could be applied clinically.

Methods

Quantitative real-time PCR experiments were conducted to determine the appropriate condition to up-regulate HO-1 gene expression. A promoter assay experiment and a microarray analysis were done to analyze signal transduction pathways to be activated in endothelial cells by ultrasound stimulation.

Results

Approximately, 33-fold up-regulation of HO-1 mRNA was observed when endothelial cells were exposed to 1-MHz ultrasound at 0.3 W/cm2 and DF 10 % for 20 s. Data obtained from promoter analysis and microarray analysis suggested that the Nrf2/StRE signal pathway was involved in the up-regulation. In addition, ultrasound stimulation to endothelial cells changed its gene expression profile so that it could modify the anti-inflammatory, antioxidant, and vasodilatory activities in addition to pro-angiogenic and vascular reconstitution activities of endothelial cells.

Conclusion

It was suggested that ultrasound stimulation of endothelial cells up-regulated HO-1 expression through intracellular oxidative stress, which subsequently changed the gene expression pattern so that it could modify vascular functions.

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Acknowledgments

The authors are thankful to Prof. Takashi Kondo and Dr. Qing Li Zhao of University of Toyama for their cooperation and support for this research. The present research was supported in part by the Research and Development Committee Program of The Japan Society of Ultrasound in Medicine, and by a Grant-in-Aid for Scientific Research (C) 24592442 from the Ministry of Education, Culture, Sports, Science and Technology.

Conflict of interest

The authors declare that there is no conflict of interest.

Ethical standard

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan

    Ryohei Ogawa

  2. Department of Urology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan

    Akihiko Watanabe & Akihiro Morii

Authors
  1. Ryohei Ogawa
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  2. Akihiko Watanabe
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  3. Akihiro Morii
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Correspondence to Ryohei Ogawa.

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Ogawa, R., Watanabe, A. & Morii, A. Ultrasound up-regulates expression of heme oxygenase-1 gene in endothelial cells. J Med Ultrasonics 42, 467–475 (2015). https://doi.org/10.1007/s10396-015-0635-3

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  • DOI: https://doi.org/10.1007/s10396-015-0635-3

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