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<p>Sepsis-induced acute kidney injury (AKI) is associated with a high mortality rate and presents a significant clinical challenge. However, effective treatment measures have not yet been established. The cholinergic anti-inflammatory pathway (CAP), a neural mechanism that regulates immune responses, has been reported to mitigate kidney injury. Although numerous studies have demonstrated the benefits of CAP activation prior to injury, its therapeutic potential after the onset of injury remains insufficiently explored. Therefore, this study aimed to evaluate the renoprotective effects of CAP activation after the onset of lipopolysaccharide (LPS)-induced AKI. LPS (5&#xa0;mg/kg) was administered to C57BL/6 wild-type mice to induce AKI. Subsequently, GTS-21&#xa0;(10&#xa0;mg/kg), a selective α7 nicotinic acetylcholine receptor agonist, was administered to assess its anti-inflammatory and renoprotective effects. In RAW 264.7 and U937-derived macrophages, LPS-induced inflammation was treated with GTS-21, and its effects were evaluated. RNA sequencing was performed to elucidate the underlying molecular mechanisms. Even after the onset of LPS-induced AKI, the administration of GTS-21 demonstrated anti-inflammatory and renoprotective effects. In macrophages, the LPS-induced increase in TNF-α was suppressed by GTS-21 (50&#xa0;μM) administration. Furthermore, CCL2 expression in macrophages might be involved in mediating these effects.</p>

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α7 nicotinic acetylcholine receptor agonist attenuates lipopolysaccharide-induced acute kidney injury in mice by reducing CCL2 expression in macrophages

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月14日

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  • Sayumi Matsuo,
  • Rie Uni,
  • Chia-Hsien Wu,
  • Yasuna Nakamura,
  • Ryusuke Umene,
  • Bongkod Surattichaiyakul,
  • Masaomi Nangaku,
  • Reiko Inagi,
  • Tomoya Nishino,
  • Tsuyoshi Inoue

摘要

Sepsis-induced acute kidney injury (AKI) is associated with a high mortality rate and presents a significant clinical challenge. However, effective treatment measures have not yet been established. The cholinergic anti-inflammatory pathway (CAP), a neural mechanism that regulates immune responses, has been reported to mitigate kidney injury. Although numerous studies have demonstrated the benefits of CAP activation prior to injury, its therapeutic potential after the onset of injury remains insufficiently explored. Therefore, this study aimed to evaluate the renoprotective effects of CAP activation after the onset of lipopolysaccharide (LPS)-induced AKI. LPS (5 mg/kg) was administered to C57BL/6 wild-type mice to induce AKI. Subsequently, GTS-21 (10 mg/kg), a selective α7 nicotinic acetylcholine receptor agonist, was administered to assess its anti-inflammatory and renoprotective effects. In RAW 264.7 and U937-derived macrophages, LPS-induced inflammation was treated with GTS-21, and its effects were evaluated. RNA sequencing was performed to elucidate the underlying molecular mechanisms. Even after the onset of LPS-induced AKI, the administration of GTS-21 demonstrated anti-inflammatory and renoprotective effects. In macrophages, the LPS-induced increase in TNF-α was suppressed by GTS-21 (50 μM) administration. Furthermore, CCL2 expression in macrophages might be involved in mediating these effects.