Cargando…
PGI(2) Analog Attenuates Salt-Induced Renal Injury through the Inhibition of Inflammation and Rac1-MR Activation
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 I(2) (PGI(2)) analog, in Dahl salt-sensitive (D...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353033/ https://www.ncbi.nlm.nih.gov/pubmed/32580367 http://dx.doi.org/10.3390/ijms21124433 |
_version_ | 1783557780337065984 |
---|---|
author | Hirohama, Daigoro Kawarazaki, Wakako Nishimoto, Mitsuhiro Ayuzawa, Nobuhiro Marumo, Takeshi Shibata, Shigeru Fujita, Toshiro |
author_facet | Hirohama, Daigoro Kawarazaki, Wakako Nishimoto, Mitsuhiro Ayuzawa, Nobuhiro Marumo, Takeshi Shibata, Shigeru Fujita, Toshiro |
author_sort | Hirohama, Daigoro |
collection | PubMed |
description | 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 I(2) (PGI(2)) 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 PGI(2). 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. |
format | Online Article Text |
id | pubmed-7353033 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-73530332020-07-15 PGI(2) Analog Attenuates Salt-Induced Renal Injury through the Inhibition of Inflammation and Rac1-MR Activation Hirohama, Daigoro Kawarazaki, Wakako Nishimoto, Mitsuhiro Ayuzawa, Nobuhiro Marumo, Takeshi Shibata, Shigeru Fujita, Toshiro Int J Mol Sci Article 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 I(2) (PGI(2)) 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 PGI(2). 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. MDPI 2020-06-22 /pmc/articles/PMC7353033/ /pubmed/32580367 http://dx.doi.org/10.3390/ijms21124433 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Hirohama, Daigoro Kawarazaki, Wakako Nishimoto, Mitsuhiro Ayuzawa, Nobuhiro Marumo, Takeshi Shibata, Shigeru Fujita, Toshiro PGI(2) Analog Attenuates Salt-Induced Renal Injury through the Inhibition of Inflammation and Rac1-MR Activation |
title | PGI(2) Analog Attenuates Salt-Induced Renal Injury through the Inhibition of Inflammation and Rac1-MR Activation |
title_full | PGI(2) Analog Attenuates Salt-Induced Renal Injury through the Inhibition of Inflammation and Rac1-MR Activation |
title_fullStr | PGI(2) Analog Attenuates Salt-Induced Renal Injury through the Inhibition of Inflammation and Rac1-MR Activation |
title_full_unstemmed | PGI(2) Analog Attenuates Salt-Induced Renal Injury through the Inhibition of Inflammation and Rac1-MR Activation |
title_short | PGI(2) Analog Attenuates Salt-Induced Renal Injury through the Inhibition of Inflammation and Rac1-MR Activation |
title_sort | pgi(2) analog attenuates salt-induced renal injury through the inhibition of inflammation and rac1-mr activation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353033/ https://www.ncbi.nlm.nih.gov/pubmed/32580367 http://dx.doi.org/10.3390/ijms21124433 |
work_keys_str_mv | AT hirohamadaigoro pgi2analogattenuatessaltinducedrenalinjurythroughtheinhibitionofinflammationandrac1mractivation AT kawarazakiwakako pgi2analogattenuatessaltinducedrenalinjurythroughtheinhibitionofinflammationandrac1mractivation AT nishimotomitsuhiro pgi2analogattenuatessaltinducedrenalinjurythroughtheinhibitionofinflammationandrac1mractivation AT ayuzawanobuhiro pgi2analogattenuatessaltinducedrenalinjurythroughtheinhibitionofinflammationandrac1mractivation AT marumotakeshi pgi2analogattenuatessaltinducedrenalinjurythroughtheinhibitionofinflammationandrac1mractivation AT shibatashigeru pgi2analogattenuatessaltinducedrenalinjurythroughtheinhibitionofinflammationandrac1mractivation AT fujitatoshiro pgi2analogattenuatessaltinducedrenalinjurythroughtheinhibitionofinflammationandrac1mractivation |