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<p>Renal congestion is a key factor in renal dysfunction associated with heart failure. We previously reported that renal congestion worsened renal ischemia-reperfusion in a murine model. However, its impact on sepsis-associated acute kidney injury (SA-AKI), the leading cause of AKI, remains unclear. Therefore, we herein investigated the mechanisms by which renal congestion exacerbates SA-AKI, with a focus on Toll-like receptor (TLR) 2. After inducing sepsis with cecal ligation and puncture (CLP) in a unilateral renal congestion model, transient blood pressure reductions and persistent renal vein dilation were observed. A histological analysis showed increased fibrosis and its markers in congested kidneys post-CLP. Acute phase results revealed extensive tubular damage, macrophage infiltration, TLR2 up-regulation, and elevated high mobility group box 1 (HMGB1) levels. In TLR2-knockout mice, exacerbation of tissue fibrosis by renal congestion was attenuated after CLP. In vitro, oxidative stress and hypoxia up-regulated TLR2 expression. Collectively, these results suggest that renal congestion and sepsis synergistically worsened renal damage, likely through hypoxia and the oxidative stress-induced activation of the TLR2 pathway.</p>

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Toll like receptor 2 mediated exacerbation of sepsis associated acute kidney injury by renal congestion in mice

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月1日

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  • Itaru Nakamura,
  • Minato Umehara,
  • Aya Yagi-Tomita,
  • Satomi Yamamoto,
  • Shinji Sawai,
  • Masashi Nakamura,
  • Atsushi Minamida,
  • Hiroko Yamauchi-Sawada,
  • Yasuto Sunahara,
  • Yayoi Matoba,
  • Natsuko Okuno-Ozeki,
  • Kunihiro Nakai,
  • Tomohiro Nakata,
  • Takashi Kitani,
  • Noriyuki Yamashita,
  • Kazumi Komaki,
  • Yuhei Kirita,
  • Keiichi Tamagaki,
  • Satoaki Matoba,
  • Tetsuro Kusaba

摘要

Renal congestion is a key factor in renal dysfunction associated with heart failure. We previously reported that renal congestion worsened renal ischemia-reperfusion in a murine model. However, its impact on sepsis-associated acute kidney injury (SA-AKI), the leading cause of AKI, remains unclear. Therefore, we herein investigated the mechanisms by which renal congestion exacerbates SA-AKI, with a focus on Toll-like receptor (TLR) 2. After inducing sepsis with cecal ligation and puncture (CLP) in a unilateral renal congestion model, transient blood pressure reductions and persistent renal vein dilation were observed. A histological analysis showed increased fibrosis and its markers in congested kidneys post-CLP. Acute phase results revealed extensive tubular damage, macrophage infiltration, TLR2 up-regulation, and elevated high mobility group box 1 (HMGB1) levels. In TLR2-knockout mice, exacerbation of tissue fibrosis by renal congestion was attenuated after CLP. In vitro, oxidative stress and hypoxia up-regulated TLR2 expression. Collectively, these results suggest that renal congestion and sepsis synergistically worsened renal damage, likely through hypoxia and the oxidative stress-induced activation of the TLR2 pathway.