Centre de Néphrologie et Transplantation Rénale, Assistance Publique-Hôpitaux de Marseille, Hôpital de La Conception, 147 Boulevard Baille, 13005 Marseille, France.
Centre de Recherche en Cardiovasculaire et Nutrition (C2VN), Institut de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche pour l'Agriculture, l'Alimentation et l'Environnement (INRAE), Aix Marseille University, 13005 Marseille, France.
Int J Mol Sci. 2022 Feb 21;23(4):2369. doi: 10.3390/ijms23042369.
In patients with chronic kidney disease (CKD) and in animal models of CKD, the transcription factor Aryl Hydrocabon Receptor (AhR) is overactivated. In addition to the canonical AhR targets constituting the AhR signature, numerous other genes are regulated by this factor. We identified neuronal pentraxin 1 (NPTX1) as a new AhR target. Belonging to the inflammatory protein family, NPTX1 seems of prime interest regarding the inflammatory state observed in CKD. Endothelial cells were exposed to tryptophan-derived toxins, indoxyl sulfate (IS) and indole-3-acetic acid (IAA). The adenine mouse model of CKD was used to analyze NPTX1 expression in the burden of uremia. NPTX1 expression was quantified by RT-PCR and western blot. AhR involvement was analyzed using silencing RNA. We found that IS and IAA upregulated NPTX1 expression in an AhR-dependent way. Furthermore, this effect was not restricted to uremic indolic toxins since the dioxin 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and the tryptophan photoproduct 6-formylindolo[3,2-b]carbazole (FICZ) do the same. In CKD mice, NPTX1 expression was increased in the aorta. Therefore, NPTX1 is a new target of AhR and further work is necessary to elucidate its exact role during CKD.
在患有慢性肾脏病（CKD）的患者和 CKD 的动物模型中，芳香烃受体（AhR）转录因子过度激活。除了构成 AhR 特征的典型 AhR 靶标外，该因子还调节许多其他基因。我们确定神经元五聚素 1（NPTX1）是一个新的 AhR 靶标。属于炎症蛋白家族，NPTX1 似乎是与 CKD 中观察到的炎症状态有关的主要关注点。将内皮细胞暴露于色氨酸衍生的毒素，吲哚硫酸（IS）和吲哚-3-乙酸（IAA）中。使用腺嘌呤小鼠 CKD 模型分析尿毒症负担中的 NPTX1 表达。通过 RT-PCR 和 Western blot 定量 NPTX1 表达。使用沉默 RNA 分析 AhR 的参与。我们发现 IS 和 IAA 以 AhR 依赖的方式上调 NPTX1 表达。此外，这种作用不仅限于尿毒症吲哚类毒素，因为二恶英 2,3,7,8-四氯二苯并对二恶英（TCDD）和色氨酸光产物 6-甲酰基吲哚[3,2-b]咔唑（FICZ）也是如此。在 CKD 小鼠中，NPTX1 表达在主动脉中增加。因此，NPTX1 是 AhR 的一个新靶标，需要进一步研究来阐明其在 CKD 期间的确切作用。
