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

Proceedings of the Japan Academy, Series B. Physical and Biological Sciences

article

Changhai SU¹  Gang LI²  Chao GU²  Yuan GAO²  Ruilan HAN²  Min GUO¹  Hong LIU²  Jie GAO²  Yang LIU²  Bing LI²  Lijun SUN²  Ren BU²  Yang LIU¹  Jian HAO⁴  Yan MENG⁴  Ming AN⁵  Xiaodong CAO⁶ 

[1] Department of Clinical Pharmacy, Ordos Central Hospital;Department of Pharmacology, College of Pharmacy, Inner Mongolian Medical University;Mongolian Medicine Collaborative Innovation Center, Inner Mongolia Medical University;Renal Division, The First Affiliated Hospital of Inner Mongolia Medical University;Department of Pharmaceutical analysis, School of Pharmacy, Baotou Medical College;Department of Pharmacology, GLP Center, Inner Mongolian Medical University

关键词: metabolomics;    end-stage renal disease;    lanthanum hydroxide;    vascular calcification;    signal pathway;   

DOI  :  10.2183/pjab.98.019

学科分类：物理（综合）

来源: Japan Academy

【 摘 要 】

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.

【 授权许可】

Unknown