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Aldosterone stimulates nuclear factor-kappa B activity and transcription of intercellular adhesion molecule-1 and connective tissue growth factor in rat mesangial cells via serum- and glucocorticoid-inducible protein kinase-1

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  • The 36th IUPS Satellite Symposium: The Kidney and Hypertension
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Abstract

Several clinical and experimental data support the hypothesis that aldosterone contributes to the progression of renal injury. To determine the signaling pathway of aldosterone in relation to fibrosis and inflammation in mesangial cells, we investigated the effects of aldosterone on expression and activation of serum- and glucocorticoid-inducible protein kinase-1 (SGK1), the activation of nuclear factor-kappa B (NF-κB activation, and the expressions of intercellular adhesion molecule-1 (ICAM-1) and connective tissue growth factor (CTGF). Aldosterone stimulated SGK1 expression, phosphorylation (Ser-256), and kinase activity. The increments of phosphorylation and expression of SGK1 induced by aldosterone were inhibited by mineralocorticoid receptor (MR) inhibitor (eplerenone). Aldosterone stimulated NF-κB activity measured by NF-κB responsive elements, luciferase assay, and the levels of inhibitor of kappa B (IκB) phosphorylation. This aldosterone-induced activation of NF-κB was inhibited by the transfection of dominant-negative SGK1. Furthermore, aldosterone augmented the promoter activities and protein expressions of ICAM-1 and CTGF. The effects of aldosterone on ICAM-1 and CTGF promoter activities and protein expressions were inhibited by the transfection of dominant-negative SGK1 and dominant-negative IκBα. We also found that the MR antagonist significantly ameliorated the glomerular injury and enhancements in SGK1, ICAM-1, and CTGF expressions induced by 1% sodium chloride and aldosterone in vivo. In conclusion, our findings suggest that aldosterone stimulates ICAM-1 and CTGF transcription via activation of SGK1 and NF-κB, which may be involved in the progression of aldosterone-induced mesangial fibrosis and inflammation. MR antagonists may serve as useful therapeutic targets for the treatment of glomerular inflammatory disease.

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Acknowledgments

We thank Dr. E.G. Krebs, Dr. Paul T. van der Saag, and Dr. B. Hemmings for providing plasmids. This work was supported by the Research fund of Mitsukoshi Health and Welfare foundation, Mochida Memorial foundation, Naito Memorial foundation, and a grant from the Ministry of Education, Science, Culture and Sports of Japan (to Y.T).

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Authors and Affiliations

  1. Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, Kohashu, Oko-cho, Nankoku, 783-8505, Japan

    Yoshio Terada, Satoko Ueda, Kazu Hamada, Yoshiko Shimamura, Koji Ogata, Kosuke Inoue, Yoshinori Taniguchi, Toru Kagawa, Taro Horino & Toshihiro Takao

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  1. Yoshio Terada
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Correspondence to Yoshio Terada.

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Terada, Y., Ueda, S., Hamada, K. et al. Aldosterone stimulates nuclear factor-kappa B activity and transcription of intercellular adhesion molecule-1 and connective tissue growth factor in rat mesangial cells via serum- and glucocorticoid-inducible protein kinase-1. Clin Exp Nephrol 16, 81–88 (2012). https://doi.org/10.1007/s10157-011-0498-x

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