(Pro)renin receptor blocker improves survival of rats with sepsis

Yuki Hirano, Hiroya Takeuchi, Koichi Suda, Tomoko Hagiwara, Taku Miyasho, Yoshio Kawamura, Shingo Yamada, Takashi Oyama, Tsunehiro Takahashi, Norihito Wada, Yoshiro Saikawa, Atsuhiro Ichihara, Yuukou Kitagawa

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background The renin-angiotensin system (RAS) affects inflammatory responses during sepsis. Nonproteolytic activation of prorenin by the (pro)renin receptor has recently been shown to stimulate the tissue RAS. In the present study, the effect of (pro)renin receptor blocker (PRRB) pretreatment on sepsis in a rat cecal ligation and puncture (CLP) model was investigated. Materials and methods Male Sprague-Dawley rats underwent CLP and were randomly divided into two groups: PRRB-treated group and control peptide-treated group. Survival was analyzed for 7 d after CLP. The serum concentrations of cytokines and high-mobility group box chromosomal protein 1 (HMGB1) were measured at three time points (0, 3, and 6 h after CLP). Hematoxylin-eosin staining and immunohistochemical staining for nonproteolytically activated prorenin and HMGB1 were performed on the cecum to assess pathologic changes found 6 h after CLP. Results Treatment with PRRB improved the survival rate of the post-CLP septic rats (P = 0.023). PRRB also significantly reduced serum tumor necrosis factor-α, interleukin-1β, and HMGB1 levels 6 h after CLP. In CLP rats that were treated with control peptide, the expression of activated prorenin was elevated in peritoneal foam cells. Moreover, expression of HMGB1 was increased in peritoneal inflammatory cells. In contrast, both were markedly suppressed in CLP rats that were treated with PRRB. Conclusions PRRB significantly improved the survival rate of rats with clinically relevant sepsis, possibly by attenuating a sepsis-induced systemic inflammatory response. We propose that overactivation of the RAS by activation of prorenin in foam cells may be a significant contributor to sepsis.

Original languageEnglish
Pages (from-to)269-277
Number of pages9
JournalJournal of Surgical Research
Volume186
Issue number1
DOIs
Publication statusPublished - 2014 Jan

Fingerprint

Renin
Sepsis
Punctures
Ligation
High Mobility Group Proteins
HMGB1 Protein
Renin-Angiotensin System
Foam Cells
Staining and Labeling
Peptides
Cecum
Hematoxylin
Eosine Yellowish-(YS)
Serum
Interleukin-1
Sprague Dawley Rats
Tumor Necrosis Factor-alpha
Cytokines
Control Groups

Keywords

  • (Pro)renin receptor
  • Cecal ligation and puncture
  • Cytokine
  • Foam cell
  • High-mobility group box chromosomal protein 1
  • Prorenin
  • Renin-angiotensin system
  • Sepsis

ASJC Scopus subject areas

  • Surgery

Cite this

Hirano, Y., Takeuchi, H., Suda, K., Hagiwara, T., Miyasho, T., Kawamura, Y., ... Kitagawa, Y. (2014). (Pro)renin receptor blocker improves survival of rats with sepsis. Journal of Surgical Research, 186(1), 269-277. https://doi.org/10.1016/j.jss.2013.08.004

(Pro)renin receptor blocker improves survival of rats with sepsis. / Hirano, Yuki; Takeuchi, Hiroya; Suda, Koichi; Hagiwara, Tomoko; Miyasho, Taku; Kawamura, Yoshio; Yamada, Shingo; Oyama, Takashi; Takahashi, Tsunehiro; Wada, Norihito; Saikawa, Yoshiro; Ichihara, Atsuhiro; Kitagawa, Yuukou.

In: Journal of Surgical Research, Vol. 186, No. 1, 01.2014, p. 269-277.

Research output: Contribution to journalArticle

Hirano, Y, Takeuchi, H, Suda, K, Hagiwara, T, Miyasho, T, Kawamura, Y, Yamada, S, Oyama, T, Takahashi, T, Wada, N, Saikawa, Y, Ichihara, A & Kitagawa, Y 2014, '(Pro)renin receptor blocker improves survival of rats with sepsis', Journal of Surgical Research, vol. 186, no. 1, pp. 269-277. https://doi.org/10.1016/j.jss.2013.08.004
Hirano Y, Takeuchi H, Suda K, Hagiwara T, Miyasho T, Kawamura Y et al. (Pro)renin receptor blocker improves survival of rats with sepsis. Journal of Surgical Research. 2014 Jan;186(1):269-277. https://doi.org/10.1016/j.jss.2013.08.004
Hirano, Yuki ; Takeuchi, Hiroya ; Suda, Koichi ; Hagiwara, Tomoko ; Miyasho, Taku ; Kawamura, Yoshio ; Yamada, Shingo ; Oyama, Takashi ; Takahashi, Tsunehiro ; Wada, Norihito ; Saikawa, Yoshiro ; Ichihara, Atsuhiro ; Kitagawa, Yuukou. / (Pro)renin receptor blocker improves survival of rats with sepsis. In: Journal of Surgical Research. 2014 ; Vol. 186, No. 1. pp. 269-277.
@article{79412a90433e4afeb0b1be138e59e138,
title = "(Pro)renin receptor blocker improves survival of rats with sepsis",
abstract = "Background The renin-angiotensin system (RAS) affects inflammatory responses during sepsis. Nonproteolytic activation of prorenin by the (pro)renin receptor has recently been shown to stimulate the tissue RAS. In the present study, the effect of (pro)renin receptor blocker (PRRB) pretreatment on sepsis in a rat cecal ligation and puncture (CLP) model was investigated. Materials and methods Male Sprague-Dawley rats underwent CLP and were randomly divided into two groups: PRRB-treated group and control peptide-treated group. Survival was analyzed for 7 d after CLP. The serum concentrations of cytokines and high-mobility group box chromosomal protein 1 (HMGB1) were measured at three time points (0, 3, and 6 h after CLP). Hematoxylin-eosin staining and immunohistochemical staining for nonproteolytically activated prorenin and HMGB1 were performed on the cecum to assess pathologic changes found 6 h after CLP. Results Treatment with PRRB improved the survival rate of the post-CLP septic rats (P = 0.023). PRRB also significantly reduced serum tumor necrosis factor-α, interleukin-1β, and HMGB1 levels 6 h after CLP. In CLP rats that were treated with control peptide, the expression of activated prorenin was elevated in peritoneal foam cells. Moreover, expression of HMGB1 was increased in peritoneal inflammatory cells. In contrast, both were markedly suppressed in CLP rats that were treated with PRRB. Conclusions PRRB significantly improved the survival rate of rats with clinically relevant sepsis, possibly by attenuating a sepsis-induced systemic inflammatory response. We propose that overactivation of the RAS by activation of prorenin in foam cells may be a significant contributor to sepsis.",
keywords = "(Pro)renin receptor, Cecal ligation and puncture, Cytokine, Foam cell, High-mobility group box chromosomal protein 1, Prorenin, Renin-angiotensin system, Sepsis",
author = "Yuki Hirano and Hiroya Takeuchi and Koichi Suda and Tomoko Hagiwara and Taku Miyasho and Yoshio Kawamura and Shingo Yamada and Takashi Oyama and Tsunehiro Takahashi and Norihito Wada and Yoshiro Saikawa and Atsuhiro Ichihara and Yuukou Kitagawa",
year = "2014",
month = "1",
doi = "10.1016/j.jss.2013.08.004",
language = "English",
volume = "186",
pages = "269--277",
journal = "Journal of Surgical Research",
issn = "0022-4804",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - (Pro)renin receptor blocker improves survival of rats with sepsis

AU - Hirano, Yuki

AU - Takeuchi, Hiroya

AU - Suda, Koichi

AU - Hagiwara, Tomoko

AU - Miyasho, Taku

AU - Kawamura, Yoshio

AU - Yamada, Shingo

AU - Oyama, Takashi

AU - Takahashi, Tsunehiro

AU - Wada, Norihito

AU - Saikawa, Yoshiro

AU - Ichihara, Atsuhiro

AU - Kitagawa, Yuukou

PY - 2014/1

Y1 - 2014/1

N2 - Background The renin-angiotensin system (RAS) affects inflammatory responses during sepsis. Nonproteolytic activation of prorenin by the (pro)renin receptor has recently been shown to stimulate the tissue RAS. In the present study, the effect of (pro)renin receptor blocker (PRRB) pretreatment on sepsis in a rat cecal ligation and puncture (CLP) model was investigated. Materials and methods Male Sprague-Dawley rats underwent CLP and were randomly divided into two groups: PRRB-treated group and control peptide-treated group. Survival was analyzed for 7 d after CLP. The serum concentrations of cytokines and high-mobility group box chromosomal protein 1 (HMGB1) were measured at three time points (0, 3, and 6 h after CLP). Hematoxylin-eosin staining and immunohistochemical staining for nonproteolytically activated prorenin and HMGB1 were performed on the cecum to assess pathologic changes found 6 h after CLP. Results Treatment with PRRB improved the survival rate of the post-CLP septic rats (P = 0.023). PRRB also significantly reduced serum tumor necrosis factor-α, interleukin-1β, and HMGB1 levels 6 h after CLP. In CLP rats that were treated with control peptide, the expression of activated prorenin was elevated in peritoneal foam cells. Moreover, expression of HMGB1 was increased in peritoneal inflammatory cells. In contrast, both were markedly suppressed in CLP rats that were treated with PRRB. Conclusions PRRB significantly improved the survival rate of rats with clinically relevant sepsis, possibly by attenuating a sepsis-induced systemic inflammatory response. We propose that overactivation of the RAS by activation of prorenin in foam cells may be a significant contributor to sepsis.

AB - Background The renin-angiotensin system (RAS) affects inflammatory responses during sepsis. Nonproteolytic activation of prorenin by the (pro)renin receptor has recently been shown to stimulate the tissue RAS. In the present study, the effect of (pro)renin receptor blocker (PRRB) pretreatment on sepsis in a rat cecal ligation and puncture (CLP) model was investigated. Materials and methods Male Sprague-Dawley rats underwent CLP and were randomly divided into two groups: PRRB-treated group and control peptide-treated group. Survival was analyzed for 7 d after CLP. The serum concentrations of cytokines and high-mobility group box chromosomal protein 1 (HMGB1) were measured at three time points (0, 3, and 6 h after CLP). Hematoxylin-eosin staining and immunohistochemical staining for nonproteolytically activated prorenin and HMGB1 were performed on the cecum to assess pathologic changes found 6 h after CLP. Results Treatment with PRRB improved the survival rate of the post-CLP septic rats (P = 0.023). PRRB also significantly reduced serum tumor necrosis factor-α, interleukin-1β, and HMGB1 levels 6 h after CLP. In CLP rats that were treated with control peptide, the expression of activated prorenin was elevated in peritoneal foam cells. Moreover, expression of HMGB1 was increased in peritoneal inflammatory cells. In contrast, both were markedly suppressed in CLP rats that were treated with PRRB. Conclusions PRRB significantly improved the survival rate of rats with clinically relevant sepsis, possibly by attenuating a sepsis-induced systemic inflammatory response. We propose that overactivation of the RAS by activation of prorenin in foam cells may be a significant contributor to sepsis.

KW - (Pro)renin receptor

KW - Cecal ligation and puncture

KW - Cytokine

KW - Foam cell

KW - High-mobility group box chromosomal protein 1

KW - Prorenin

KW - Renin-angiotensin system

KW - Sepsis

UR - http://www.scopus.com/inward/record.url?scp=84890031347&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84890031347&partnerID=8YFLogxK

U2 - 10.1016/j.jss.2013.08.004

DO - 10.1016/j.jss.2013.08.004

M3 - Article

C2 - 24011922

AN - SCOPUS:84890031347

VL - 186

SP - 269

EP - 277

JO - Journal of Surgical Research

JF - Journal of Surgical Research

SN - 0022-4804

IS - 1

ER -