Emodin Inhibits the Indoxyl Sulfate-Induced trans-Differentiation of Vascular Smooth Muscle Cells through Upregulating Thrombospondin-1.

IF 1.8 4区医学 Q3 PERIPHERAL VASCULAR DISEASE

Journal of Vascular Research Pub Date : 2023-01-01 Epub Date: 2023-09-05 DOI:10.1159/000532028

Weidong Zhang, Jing Chen, Xiao Tan, Pan Zhang, Xialian Xu, Xiaoqiang Ding, Shuan Zhao, Shi Jin

{"title":"Emodin Inhibits the Indoxyl Sulfate-Induced trans-Differentiation of Vascular Smooth Muscle Cells through Upregulating Thrombospondin-1.","authors":"Weidong Zhang, Jing Chen, Xiao Tan, Pan Zhang, Xialian Xu, Xiaoqiang Ding, Shuan Zhao, Shi Jin","doi":"10.1159/000532028","DOIUrl":null,"url":null,"abstract":"Background: Indoxyl sulfate (IS) is a protein-bound uremic toxin with vascular toxicity. The primary cause of death in uremic patients on maintenance hemodialysis is vascular disease, and it had been reported that vascular smooth muscle cells (VSMCs) trans-differentiation (VT) plays a vital role in the context of vascular diseases, but the underlying mechanisms remain obscure. Thrombospondin-1 (TSP-1) participates in vascular calcification by keeping the balance of extracellular matrix, but its role in IS-induced VT is unclear.Methods: In this study, clinical specimens, animal models, and in vitro VSMCs were used to investigate the role of TSP-1 in IS induced VT and the potential therapeutic methods.Results: We found that TSP-1 was significantly decreased in arterial samples from uremic patients, animal models, and in VSMCs after IS treatment. Downregulation of TSP-1 sufficiently induced the trans-differentiation genotypes of VSMCs.Conclusion: Emodin, the main monomer extracted from rhubarb, could alleviate IS-induced VT in vitro by upregulating TSP-1. Taken together, IS induces VT by downregulating TSP-1. Emodin might be a candidate drug to alleviate VT under IS treatment.","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":" ","pages":"193-203"},"PeriodicalIF":1.8000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614470/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Vascular Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000532028","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/9/5 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"PERIPHERAL VASCULAR DISEASE","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Indoxyl sulfate (IS) is a protein-bound uremic toxin with vascular toxicity. The primary cause of death in uremic patients on maintenance hemodialysis is vascular disease, and it had been reported that vascular smooth muscle cells (VSMCs) trans-differentiation (VT) plays a vital role in the context of vascular diseases, but the underlying mechanisms remain obscure. Thrombospondin-1 (TSP-1) participates in vascular calcification by keeping the balance of extracellular matrix, but its role in IS-induced VT is unclear.

Methods: In this study, clinical specimens, animal models, and in vitro VSMCs were used to investigate the role of TSP-1 in IS induced VT and the potential therapeutic methods.

Results: We found that TSP-1 was significantly decreased in arterial samples from uremic patients, animal models, and in VSMCs after IS treatment. Downregulation of TSP-1 sufficiently induced the trans-differentiation genotypes of VSMCs.

Conclusion: Emodin, the main monomer extracted from rhubarb, could alleviate IS-induced VT in vitro by upregulating TSP-1. Taken together, IS induces VT by downregulating TSP-1. Emodin might be a candidate drug to alleviate VT under IS treatment.

查看原文本刊更多论文

大黄素通过上调血小板反应蛋白-1抑制硫酸吲哚酚诱导的血管平滑肌细胞反式分化。

背景：硫酸吲哚酚（IS）是一种具有血管毒性的蛋白结合尿毒症毒素。尿毒症维持性血液透析患者死亡的主要原因是血管疾病，据报道，血管平滑肌细胞（VSMCs）转分化（VT）在血管疾病中起着至关重要的作用，但其潜在机制尚不清楚。血小板反应蛋白-1（TSP-1）通过维持细胞外基质的平衡参与血管钙化，但其在IS诱导的室性心动过速中的作用尚不清楚。方法：本研究采用临床标本、动物模型和体外VSMCs研究TSP-1在IS诱导的室性心动过速中的作用以及潜在的治疗方法。结果：我们发现，在尿毒症患者的动脉样本、动物模型和IS治疗后的VSMCs中，TSP-1显著降低。TSP-1的下调充分诱导了VSMCs的反式分化基因型。结论：大黄中提取的主要单体大黄素可通过上调TSP-1在体外减轻IS诱导的室性心动过速。综合来看，IS通过下调TSP-1诱导室性心动过速。大黄素可能是缓解IS治疗下室性心动过速的候选药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Vascular Research 医学-生理学

CiteScore

3.40

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： The ''Journal of Vascular Research'' publishes original articles and reviews of scientific excellence in vascular and microvascular biology, physiology and pathophysiology. The scope of the journal covers a broad spectrum of vascular and lymphatic research, including vascular structure, vascular function, haemodynamics, mechanics, cell signalling, intercellular communication, growth and differentiation. JVR''s ''Vascular Update'' series regularly presents state-of-the-art reviews on hot topics in vascular biology. Manuscript processing times are, consistent with stringent review, kept as short as possible due to electronic submission. All articles are published online first, ensuring rapid publication. The ''Journal of Vascular Research'' is the official journal of the European Society for Microcirculation. A biennial prize is awarded to the authors of the best paper published in the journal over the previous two years, thus encouraging young scientists working in the exciting field of vascular biology to publish their findings.