Sinomenine attenuates uremia vascular calcification by miR-143-5p

Abstract Vascular calcification is considered to be a killer of the cardiovascular system, involved inflammation and immunity. There is no approved therapeutic strategy for the prevention of vascular calcification. Sinomenine exhibited anti-inflammatory and immunosuppressive effects. Objective of th...

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Main Authors: Fengyi Yu, Zhong Peng, Ning Gao, Zixu Tang, Zihao Liao, Song Zhao, Shuzhu Zhong, Gloria Umwiza, Hong Huang, Wei Long, Zhangxiu He
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-86055-2
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author Fengyi Yu
Zhong Peng
Ning Gao
Zixu Tang
Zihao Liao
Song Zhao
Shuzhu Zhong
Gloria Umwiza
Hong Huang
Wei Long
Zhangxiu He
author_facet Fengyi Yu
Zhong Peng
Ning Gao
Zixu Tang
Zihao Liao
Song Zhao
Shuzhu Zhong
Gloria Umwiza
Hong Huang
Wei Long
Zhangxiu He
author_sort Fengyi Yu
collection DOAJ
description Abstract Vascular calcification is considered to be a killer of the cardiovascular system, involved inflammation and immunity. There is no approved therapeutic strategy for the prevention of vascular calcification. Sinomenine exhibited anti-inflammatory and immunosuppressive effects. Objective of this study was to investigate the effect of sinomenine in vascular calcification and its potential molecular mechanism. Adenine-induced uremic rats were constructed and administrated with sinomenine. Optical clearing of aortas, alizarin red staining, von Kossa staining, calcification quantification, micro-CT analyses of vascular calcification were performed to analyze calcification in aortas. Administration of 40 mg/kg/d sinomenine effectively alleviated vascular calcification in uremic rats. The miRNA sequencing revealed differentially expressed miRNAs in aortas and bioinformatic analysis assisted with miRNA screening. We screened 9 differential expressed miRNAs and their predicted target genes. By qRT-PCR, we validated that the expression of rno-miR-143-5p was corresponding to our prediction. Sinomenine inhibited vascular smooth muscle cells (VSMCs) calcification, accompanied with miR-143-5p upregulation. MiR-143-5p mimic decreased VSMCs calcification in high phosphate condition. On the contrary, miR-143-5p inhibitor increased VSMCs calcification in high phosphate condition, which was inhibited by sinomenine. In chronic kidney disease patients with vascular calcification, the expression level of circulating miR-143-5p was lower than those without vascular calcification. Sinomenine significantly inhibited vascular calcification in VSMCs and uremic rat. MiR-143-5p was one of the collection of miRNAs modified by sinomenine in vascular calcification. Reduction of miR-143-5p in VSMCs was not only a concomitant phenomenon in pro-calcification condition but also contribute to VSMCs calcification. Circulating miR-143-5p was supposed to be a potential biomarker for vascular calcification in chronic kidney disease patients. In conclusion, sinomenine effectively alleviated vascular calcification, which was attributed to miR-143-5p regulation partly.
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publishDate 2025-01-01
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spelling doaj-art-2e1bfa0e343342fd9e3e53916856a4502025-01-19T12:23:45ZengNature PortfolioScientific Reports2045-23222025-01-0115111710.1038/s41598-025-86055-2Sinomenine attenuates uremia vascular calcification by miR-143-5pFengyi Yu0Zhong Peng1Ning Gao2Zixu Tang3Zihao Liao4Song Zhao5Shuzhu Zhong6Gloria Umwiza7Hong Huang8Wei Long9Zhangxiu He10Department of Nephrology, Yiyang Central HospitalDepartment of Gastroenterology, Yiyang Central HospitalDepartment of Nephrology, Yiyang Central HospitalDepartment of Nephrology, Yiyang Central HospitalDepartment of Nephrology, Yiyang Central HospitalDepartment of Nephrology, Yiyang Central HospitalDepartment of Nephrology, Yiyang Central HospitalDepartment of Nephrology, Yiyang Central HospitalHengyang Medical School, University of South ChinaDepartment of Nephrology, Yiyang Central HospitalDepartment of Nephrology, Yiyang Central HospitalAbstract Vascular calcification is considered to be a killer of the cardiovascular system, involved inflammation and immunity. There is no approved therapeutic strategy for the prevention of vascular calcification. Sinomenine exhibited anti-inflammatory and immunosuppressive effects. Objective of this study was to investigate the effect of sinomenine in vascular calcification and its potential molecular mechanism. Adenine-induced uremic rats were constructed and administrated with sinomenine. Optical clearing of aortas, alizarin red staining, von Kossa staining, calcification quantification, micro-CT analyses of vascular calcification were performed to analyze calcification in aortas. Administration of 40 mg/kg/d sinomenine effectively alleviated vascular calcification in uremic rats. The miRNA sequencing revealed differentially expressed miRNAs in aortas and bioinformatic analysis assisted with miRNA screening. We screened 9 differential expressed miRNAs and their predicted target genes. By qRT-PCR, we validated that the expression of rno-miR-143-5p was corresponding to our prediction. Sinomenine inhibited vascular smooth muscle cells (VSMCs) calcification, accompanied with miR-143-5p upregulation. MiR-143-5p mimic decreased VSMCs calcification in high phosphate condition. On the contrary, miR-143-5p inhibitor increased VSMCs calcification in high phosphate condition, which was inhibited by sinomenine. In chronic kidney disease patients with vascular calcification, the expression level of circulating miR-143-5p was lower than those without vascular calcification. Sinomenine significantly inhibited vascular calcification in VSMCs and uremic rat. MiR-143-5p was one of the collection of miRNAs modified by sinomenine in vascular calcification. Reduction of miR-143-5p in VSMCs was not only a concomitant phenomenon in pro-calcification condition but also contribute to VSMCs calcification. Circulating miR-143-5p was supposed to be a potential biomarker for vascular calcification in chronic kidney disease patients. In conclusion, sinomenine effectively alleviated vascular calcification, which was attributed to miR-143-5p regulation partly.https://doi.org/10.1038/s41598-025-86055-2SinomenineVascular calcificationUremiaRNA-seqmicroRNAs
spellingShingle Fengyi Yu
Zhong Peng
Ning Gao
Zixu Tang
Zihao Liao
Song Zhao
Shuzhu Zhong
Gloria Umwiza
Hong Huang
Wei Long
Zhangxiu He
Sinomenine attenuates uremia vascular calcification by miR-143-5p
Scientific Reports
Sinomenine
Vascular calcification
Uremia
RNA-seq
microRNAs
title Sinomenine attenuates uremia vascular calcification by miR-143-5p
title_full Sinomenine attenuates uremia vascular calcification by miR-143-5p
title_fullStr Sinomenine attenuates uremia vascular calcification by miR-143-5p
title_full_unstemmed Sinomenine attenuates uremia vascular calcification by miR-143-5p
title_short Sinomenine attenuates uremia vascular calcification by miR-143-5p
title_sort sinomenine attenuates uremia vascular calcification by mir 143 5p
topic Sinomenine
Vascular calcification
Uremia
RNA-seq
microRNAs
url https://doi.org/10.1038/s41598-025-86055-2
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