| Literature DB >> 35908957 |
Chao Gu1, Yuan Gao1, Ruilan Han1, Min Guo2, Hong Liu1, Jie Gao1, Yang Liu2, Bing Li1, Lijun Sun1, Ren Bu1, Yang Liu2, Jian Hao3, Yan Meng3, Ming An4, Xiaodong Cao5, Changhai Su2, Gang Li1,6.
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.Entities:
Keywords: end-stage renal disease; lanthanum hydroxide; metabolomics; signal pathway; vascular calcification
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Year: 2022 PMID： 35908957 PMCID： PMC9363596 DOI： 10.2183/pjab.98.019
Source DB: PubMed Journal: Proc Jpn Acad Ser B Phys Biol Sci ISSN： 0386-2208 Impact factor: 3.945