Metabolomics of Clinical Samples Reveal the Treatment Mechanism of Lanthanum Hydroxide on Vascular Calcification in Chronic Kidney Disease

Overview

Journal Proc Jpn Acad Ser B Phys Biol Sci

Specialties Biology
Science

Date 2022 Jul 31

PMID 35908957

Authors

Chao Gu

Yuan Gao

Ruilan Han

Min Guo

Hong Liu

Jie Gao

Bing Li

Lijun Sun

Ren Bu

Yang Liu

Jian Hao

Yan Meng

Ming An

Xiaodong Cao

Changhai Su

Gang Li

Affiliations

Soon will be listed here.

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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