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
{"title":"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。","authors":"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","doi":"10.2183/pjab.98.019","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":20707,"journal":{"name":"Proceedings of the Japan Academy. Series B, Physical and Biological Sciences","volume":"98 7","pages":"361-377"},"PeriodicalIF":4.4000,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a5/b3/pjab-98-361.PMC9363596.pdf","citationCount":"1","resultStr":"{\"title\":\"Metabolomics of clinical samples reveal the treatment mechanism of lanthanum hydroxide on vascular calcification in chronic kidney disease.\",\"authors\":\"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\",\"doi\":\"10.2183/pjab.98.019\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":20707,\"journal\":{\"name\":\"Proceedings of the Japan Academy. Series B, Physical and Biological Sciences\",\"volume\":\"98 7\",\"pages\":\"361-377\"},\"PeriodicalIF\":4.4000,\"publicationDate\":\"2022-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a5/b3/pjab-98-361.PMC9363596.pdf\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Proceedings of the Japan Academy. Series B, Physical and Biological Sciences\",\"FirstCategoryId\":\"103\",\"ListUrlMain\":\"https://doi.org/10.2183/pjab.98.019\",\"RegionNum\":3,\"RegionCategory\":\"综合性期刊\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MULTIDISCIPLINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Proceedings of the Japan Academy. Series B, Physical and Biological Sciences","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.2183/pjab.98.019","RegionNum":3,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
Metabolomics of clinical samples reveal the treatment mechanism of lanthanum hydroxide on vascular calcification in chronic kidney disease.
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.
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.
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