Background

Lipopolysaccharide (LPS)-induced acute kidney injury (AKI) is associated with an abnormal immune response. Accumulating evidence has demonstrated that aquaporin 1 (AQP1) prevents kidney tissue injury in LPS-induced AKI by mediating immune response. However, the underlying mechanisms remain obscure. Macrophages as immune cells with multiple phenotypes are important mediators in tissue homeostasis and host defense. We propose that macrophage polarization is implicated in AQP1-mediated immune response.

Methods

Herein we established sepsis-induced AKI model rats through intraperitoneal injection of LPS into Wistar rats to reveal immune mechanism of damage. We also used LPS-induced mouse RAW264.7 cells to elucidate the molecular mechanism of macropage polarization.

Results

Histopathology showed that renal tubular epithelial cells in the model group were swollen, inflammatory exudation was obvious and the inflammatory factors, interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) were increased. Western blotting showed PI3K was upregulated in the model group. Serum creatinine and urea nitrogen increased after LPS injection. Renal AQP1 mRNA is downregulated and serum AQP1 protein increased first and then decreased in LPS-induced AKI rats. M2 macrophage markers (Arg-1, CD206) were increased in repair stage. In addition, treatment of murine macrophages (RAW264.7) with AQP1 siRNA resulted in decreased PI3K activation and M2 polarization, but increased IL-6 and TNF-α. Moreover, inhibiting PI3K with wortmannin imitated the results of AQP1 silencing.

Conclusions

Macrophage M2 polarization is likely the cellular mechanism underlying the anti-AKI property of AQP1, and PI3K activation is involved in the AQP1-induced M2 phenotype switch.

中文翻译：

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水通道蛋白1通过PI3K介导的巨噬细胞M2极化减轻急性肾损伤

背景

脂多糖（LPS）诱导的急性肾损伤（AKI）与异常的免疫反应相关。越来越多的证据表明，水通道蛋白1（AQP1）通过介导免疫反应来预防LPS诱导的AKI中的肾脏组织损伤。但是，基本机制仍然不清楚。巨噬细胞是具有多种表型的免疫细胞，是组织稳态和宿主防御的重要介体。我们建议巨噬细胞极化涉及AQP1介导的免疫反应。

方法

本文通过腹腔注射LPS至Wistar大鼠建立脓毒症诱导的AKI模型大鼠，以揭示其损伤的免疫机制。我们还使用LPS诱导的小鼠RAW264.7细胞阐明了大页面极化的分子机制。

结果

组织病理学显示，模型组肾小管上皮细胞肿胀，有明显的炎症渗出，炎症因子，白细胞介素-6（IL-6）和肿瘤坏死因子α（TNF-α）升高。Western blotting显示模型组中PI3K上调。LPS注射后血清肌酐和尿素氮增加。在LPS诱导的AKI大鼠中，肾脏AQP1 mRNA下调，血清AQP1蛋白先升高，然后降低。在修复阶段，M2巨噬细胞标记物（Arg-1，CD206）增加。此外，用AQP1 siRNA处理鼠巨噬细胞（RAW264.7）导致PI3K活化和M2极化降低，但IL-6和TNF-α升高。此外，用渥曼青霉素抑制PI3K模仿了AQP1沉默的结果。

结论

巨噬细胞M2极化可能是AQP1抗AKI特性的细胞机制，而PI3K激活与AQP1诱导的M2表型转换有关。