PGI2 Analog Attenuates Salt-Induced Renal Injury through the Inhibition of Inflammation and Rac1-MR Activation

DOI Web Site Research Data 1 Citations 59 References Open Access
  • Wakako Kawarazaki
    Division of Clinical Epigenetics, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo 153-8904, Japan
  • Mitsuhiro Nishimoto
    Division of Clinical Epigenetics, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo 153-8904, Japan
  • Nobuhiro Ayuzawa
    Division of Clinical Epigenetics, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo 153-8904, Japan
  • Takeshi Marumo
    Division of Clinical Epigenetics, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo 153-8904, Japan
  • Shigeru Shibata
    Division of Clinical Epigenetics, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo 153-8904, Japan
  • Daigoro Hirohama
    Division of Clinical Epigenetics, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo 153-8904, Japan
  • Toshiro Fujita
    Division of Clinical Epigenetics, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo 153-8904, Japan

Bibliographic Information

Published
2020-06-22
Resource Type
journal article
Rights Information
  • https://creativecommons.org/licenses/by/4.0/
DOI
  • 10.3390/ijms21124433
Publisher
MDPI AG

Description

<jats:p>Renal inflammation is known to be involved in salt-induced renal damage, leading to end-stage renal disease. This study aims to evaluate the role of inflammation in anti-inflammatory and renoprotective effects of beraprost sodium (BPS), a prostaglandin I2 (PGI2) analog, in Dahl salt-sensitive (DS) rats. Five-week-old male DS rats were fed a normal-salt diet (0.5% NaCl), a high-salt diet (8% NaCl), or a high-salt diet plus BPS treatment for 3 weeks. BPS treatment could inhibit marked proteinuria and renal injury in salt-loaded DS rats with elevated blood pressure, accompanied by renal inflammation suppression. Notably, high salt increased renal expression of active Rac1, followed by increased Sgk1 expressions, a downstream molecule of mineralocorticoid receptor (MR) signal, indicating salt-induced activation of Rac1-MR pathway. However, BPS administration inhibited salt-induced Rac1-MR activation as well as renal inflammation and damage, suggesting that Rac1-MR pathway is involved in anti-inflammatory and renoprotective effects of PGI2. Based upon Rac1 activated by inflammation, moreover, BPS inhibited salt-induced activation of Rac1-MR pathway by renal inflammation suppression, resulting in the attenuation of renal damage in salt-loaded DS rats. Thus, BPS is efficacious for the treatment of salt-induced renal injury.</jats:p>

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