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Aldosterone-induced osteopontin expression in vascular smooth muscle cells involves MR, ERK, and p38 MAPK

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Abstract

Osteopontin (OPN) is known to be one of the cytokines that is involved in the vascular inflammation caused by aldosterone (Ald). Previous reports have shown that Ald increases OPN expression, and the mechanisms for this remain to be clarified. In this study, we investigated how Ald increases OPN expression in the vascular smooth muscle cells (VSMCs) of rats. Ald increased OPN expression time dependently as well as dose dependently. This increase was diminished by spironolactone, a mineralocorticoid receptor (MR) antagonist. PD98059, an inhibitor of p42/44 MAPK pathway, and SB203580, an inhibitor of p38 MAPK pathway, suppressed Ald-induced OPN expression and secretion in VSMCs. VSMCs migration stimulated by aldosterone required OPN expression. In conclusion, these data suggest that Ald-induced OPN expression in VSMC is mediated by MR and signaling cascades involving ERK and p38 MAPK. These molecules may represent therapeutic targets for the prevention of pathological vascular remodeling.

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Acknowledgments

This research was supported financially by grants from the National Basic Research Program of China (2011CB503905). We thank Miao Y for technical assistance.

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Authors and Affiliations

  1. State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Vascular Biology and Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China

    Ding-Liang Zhu & Ping-Jin Gao

  2. Laboratory of Vascular Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People’s Republic of China

    Ping-Jin Gao

  3. Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, People’s Republic of China

    Ding-Liang Zhu & Ping-Jin Gao

  4. Department of Gerontology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, No. 600, Yi Shan Road, Shanghai, 200233, People’s Republic of China

    Guo-Xiang Fu, Chan-Chan Xu & Yuan Zhong

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  1. Guo-Xiang Fu
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  2. Chan-Chan Xu
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Correspondence to Ping-Jin Gao.

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Fu, GX., Xu, CC., Zhong, Y. et al. Aldosterone-induced osteopontin expression in vascular smooth muscle cells involves MR, ERK, and p38 MAPK. Endocrine 42, 676–683 (2012). https://doi.org/10.1007/s12020-012-9675-2

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  • DOI: https://doi.org/10.1007/s12020-012-9675-2

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