Metabolomics of clinical samples reveal the treatment mechanism of lanthanum hydroxide on vascular calcification in chronic kidney disease.

IF 4.4 3区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Proceedings of the Japan Academy. Series B, Physical and Biological Sciences Pub Date : 2022-01-01 DOI:10.2183/pjab.98.019

Chao Gu, Yuan Gao, Ruilan Han, Min Guo, Hong Liu, Jie Gao, Yang Liu, Bing Li, Lijun Sun, Ren Bu, Yang Liu, Jian Hao, Yan Meng, Ming An, Xiaodong Cao, Changhai Su, Gang Li

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引用次数: 1

Abstract

Previous studies showed that lanthanum hydroxide (LH) has a therapeutic effect on chronic kidney disease (CKD) and vascular calcification, which suggests that it might have clinical value. However, the target and mechanism of action of LH are unclear. Metabolomics of clinical samples can be used to predict the mechanism of drug action. In this study, metabolomic profiles in patients with end-stage renal disease (ESRD) were used to screen related signaling pathways, and we verified the influence of LH on the ROS-PI3K-AKT-mTOR-HIF-1α signaling pathway by western blotting and quantitative real-time RT-qPCR in vivo and in vitro. We found that ROS and SLC16A10 genes were activated in patients with ESRD. The SLC16A10 gene is associated with six significant metabolites (L-cysteine, L-cystine, L-isoleucine, L-arginine, L-aspartic acid, and L-phenylalanine) and the PI3K-AKT signaling pathway. The results showed that LH inhibits the ESRD process and its cardiovascular complications by inhibiting the ROS-PI3K-AKT-mTOR-HIF-1α signaling pathway. Collectively, LH may be a candidate phosphorus binder for the treatment of vascular calcification in ESRD.

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临床样品的代谢组学研究揭示了氢氧化镧对慢性肾病血管钙化的治疗机制。

既往研究表明，氢氧化镧(LH)对慢性肾脏疾病(CKD)及血管钙化有治疗作用，提示其可能具有临床应用价值。然而，LH的作用靶点和作用机制尚不清楚。临床样品的代谢组学可用于预测药物作用机制。本研究利用终末期肾病(end-stage renal disease, ESRD)患者的代谢组学谱筛选相关信号通路，通过体内外western blotting和实时定量RT-qPCR验证LH对ROS-PI3K-AKT-mTOR-HIF-1α信号通路的影响。我们发现ROS和SLC16A10基因在ESRD患者中被激活。SLC16A10基因与六种重要代谢物(l -半胱氨酸、l -胱氨酸、l -异亮氨酸、l -精氨酸、l -天冬氨酸和l -苯丙氨酸)和PI3K-AKT信号通路相关。结果表明，LH通过抑制ROS-PI3K-AKT-mTOR-HIF-1α信号通路抑制ESRD过程及其心血管并发症。总之，LH可能是治疗ESRD血管钙化的候选磷结合剂。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Proceedings of the Japan Academy. Series B, Physical and Biological Sciences 生物-综合性期刊

CiteScore

6.60

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： The Proceedings of the Japan Academy Ser. B (PJA-B) is a scientific publication of the Japan Academy with a 90-year history, and covers all branches of natural sciences, except for mathematics, which is covered by the PJA-A. It is published ten times a year and is distributed widely throughout the world and can be read and obtained free of charge through the world wide web.