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胆汁酸和法尼醇 X 受体在肾脏病理生理学中的作用。

Bile Acids and Farnesoid X Receptor in Renal Pathophysiology.

机构信息

Institut Necker Enfants Malades, INSERM U1151, CNRS UMR8253, Université Paris Cité, Paris, France,

Institut Necker Enfants Malades, INSERM U1151, CNRS UMR8253, Université Paris Cité, Paris, France.

出版信息

Nephron. 2024;148(9):618-630. doi: 10.1159/000538038. Epub 2024 Feb 27.

Abstract

BACKGROUND

Bile acids (BAs) act not only as lipids and lipid-soluble vitamin detergents but also function as signaling molecules, participating in diverse physiological processes. The identification of BA receptors in organs beyond the enterohepatic system, such as the farnesoid X receptor (FXR), has initiated inquiries into their organ-specific functions. Among these organs, the kidney prominently expresses FXR.

SUMMARY

This review provides a comprehensive overview of various BA species identified in kidneys and delves into the roles of renal apical and basolateral BA transporters. Furthermore, we explore changes in BAs and their potential implications for various renal diseases, particularly chronic kidney disease. Lastly, we center our discussion on FXR, a key BA receptor in the kidney and a potential therapeutic target for renal diseases, providing current insights into the protective mechanisms associated with FXR agonist treatments.

KEY MESSAGES

Despite the relatively low concentrations of BAs in the kidney, their presence is noteworthy, with rodents and humans exhibiting distinct renal BA compositions. Renal BA transporters efficiently facilitate either reabsorption into systemic circulation or excretion into the urine. However, adaptive changes in BA transporters are evident during cholestasis. Various renal diseases are accompanied by alterations in BA concentrations and FXR expression. Consequently, the activation of FXR in the kidney could be a promising target for mitigating kidney damage.

摘要

背景

胆汁酸(BAs)不仅作为脂质和脂溶性维生素的清洁剂发挥作用,还作为信号分子参与多种生理过程。在肠肝系统以外的器官中鉴定出 BA 受体,如法尼醇 X 受体(FXR),这引发了对其器官特异性功能的研究。在这些器官中,肾脏中高表达 FXR。

概述

本文全面概述了在肾脏中鉴定出的各种 BA 种类,并深入探讨了肾脏顶侧和基底外侧 BA 转运体的作用。此外,我们还研究了 BAs 的变化及其对各种肾脏疾病(特别是慢性肾脏病)的潜在影响。最后,我们将讨论的重点放在肾脏中的关键 BA 受体 FXR 上,以及它作为肾脏疾病治疗靶点的潜力,提供了目前对 FXR 激动剂治疗相关保护机制的深入了解。

关键信息

尽管肾脏中 BA 的浓度相对较低,但它们的存在值得关注,啮齿动物和人类的肾脏 BA 组成存在明显差异。肾脏 BA 转运体可有效地促进 BA 被重吸收回体循环或排泄到尿液中。然而,在胆汁淤积时,BA 转运体发生适应性变化。各种肾脏疾病伴随着 BA 浓度和 FXR 表达的改变。因此,激活肾脏中的 FXR 可能是减轻肾脏损伤的有希望的靶点。

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