Protective role of small extracellular vesicles derived from HUVECs treated with AGEs in diabetic vascular calcification

Abstract The pathogenesis of vascular calcification in diabetic patients remains elusive. As an effective information transmitter, small extracellular vesicles (sEVs) carry abundant microRNAs (miRNAs) that regulate the physiological and pathological states of recipient cells. In the present study, s...

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Main Authors: Bei Guo, Su-Kang Shan, Feng Xu, Xiao Lin, Fu-Xing-zi Li, Yi Wang, Qiu-Shuang Xu, Ming-Hui Zheng, Li-Min Lei, Chang-Chun Li, Zhi-Ang Zhou, Muhammad Hasnain Ehsan Ullah, Feng Wu, Xiao-Bo Liao, Ling-Qing Yuan
Format: Article
Language:English
Published: BMC 2022-07-01
Series:Journal of Nanobiotechnology
Subjects:
Online Access:https://doi.org/10.1186/s12951-022-01529-z
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author Bei Guo
Su-Kang Shan
Feng Xu
Xiao Lin
Fu-Xing-zi Li
Yi Wang
Qiu-Shuang Xu
Ming-Hui Zheng
Li-Min Lei
Chang-Chun Li
Zhi-Ang Zhou
Muhammad Hasnain Ehsan Ullah
Feng Wu
Xiao-Bo Liao
Ling-Qing Yuan
author_facet Bei Guo
Su-Kang Shan
Feng Xu
Xiao Lin
Fu-Xing-zi Li
Yi Wang
Qiu-Shuang Xu
Ming-Hui Zheng
Li-Min Lei
Chang-Chun Li
Zhi-Ang Zhou
Muhammad Hasnain Ehsan Ullah
Feng Wu
Xiao-Bo Liao
Ling-Qing Yuan
author_sort Bei Guo
collection DOAJ
description Abstract The pathogenesis of vascular calcification in diabetic patients remains elusive. As an effective information transmitter, small extracellular vesicles (sEVs) carry abundant microRNAs (miRNAs) that regulate the physiological and pathological states of recipient cells. In the present study, significant up-regulation of miR-126-5p was observed in sEVs isolated from human umbilical vein endothelial cells (HUVECs) stimulated with advanced glycation end-products (A-EC/sEVs). Intriguingly, these sEVs suppressed the osteogenic differentiation of vascular smooth muscle cells (VSMCs) by targeting BMPR1B, which encodes the receptor for BMP, thereby blocking the smad1/5/9 signalling pathway. In addition, knocking down miR-126-5p in HUVECs significantly diminished the anti-calcification effect of A-EC/sEVs in a mouse model of type 2 diabetes. Overall, miR-126-5p is highly enriched in sEVs derived from AGEs stimulated HUVECs and can target BMPR1B to negatively regulate the trans-differentiation of VSMCs both in vitro and in vivo. Graphical Abstract
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spelling doaj.art-bdc96960b2c742299c5a6a748d9e530f2022-12-22T02:22:54ZengBMCJournal of Nanobiotechnology1477-31552022-07-0120111710.1186/s12951-022-01529-zProtective role of small extracellular vesicles derived from HUVECs treated with AGEs in diabetic vascular calcificationBei Guo0Su-Kang Shan1Feng Xu2Xiao Lin3Fu-Xing-zi Li4Yi Wang5Qiu-Shuang Xu6Ming-Hui Zheng7Li-Min Lei8Chang-Chun Li9Zhi-Ang Zhou10Muhammad Hasnain Ehsan Ullah11Feng Wu12Xiao-Bo Liao13Ling-Qing Yuan14National Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South UniversityNational Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South UniversityNational Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South UniversityDepartment of Radiology, The Second Xiangya Hospital, Central South UniversityNational Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South UniversityNational Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South UniversityNational Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South UniversityNational Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South UniversityNational Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South UniversityNational Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South UniversityDepartment of Cardiovascular Surgery, The Second Xiangya Hospital, Central South UniversityNational Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South UniversityDepartment of Pathology, The Second Xiangya Hospital, Central South UniversityDepartment of Cardiovascular Surgery, The Second Xiangya Hospital, Central South UniversityNational Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South UniversityAbstract The pathogenesis of vascular calcification in diabetic patients remains elusive. As an effective information transmitter, small extracellular vesicles (sEVs) carry abundant microRNAs (miRNAs) that regulate the physiological and pathological states of recipient cells. In the present study, significant up-regulation of miR-126-5p was observed in sEVs isolated from human umbilical vein endothelial cells (HUVECs) stimulated with advanced glycation end-products (A-EC/sEVs). Intriguingly, these sEVs suppressed the osteogenic differentiation of vascular smooth muscle cells (VSMCs) by targeting BMPR1B, which encodes the receptor for BMP, thereby blocking the smad1/5/9 signalling pathway. In addition, knocking down miR-126-5p in HUVECs significantly diminished the anti-calcification effect of A-EC/sEVs in a mouse model of type 2 diabetes. Overall, miR-126-5p is highly enriched in sEVs derived from AGEs stimulated HUVECs and can target BMPR1B to negatively regulate the trans-differentiation of VSMCs both in vitro and in vivo. Graphical Abstracthttps://doi.org/10.1186/s12951-022-01529-zVascular calcificationDiabetessEVsmiR-126-5pEndothelial cells
spellingShingle Bei Guo
Su-Kang Shan
Feng Xu
Xiao Lin
Fu-Xing-zi Li
Yi Wang
Qiu-Shuang Xu
Ming-Hui Zheng
Li-Min Lei
Chang-Chun Li
Zhi-Ang Zhou
Muhammad Hasnain Ehsan Ullah
Feng Wu
Xiao-Bo Liao
Ling-Qing Yuan
Protective role of small extracellular vesicles derived from HUVECs treated with AGEs in diabetic vascular calcification
Journal of Nanobiotechnology
Vascular calcification
Diabetes
sEVs
miR-126-5p
Endothelial cells
title Protective role of small extracellular vesicles derived from HUVECs treated with AGEs in diabetic vascular calcification
title_full Protective role of small extracellular vesicles derived from HUVECs treated with AGEs in diabetic vascular calcification
title_fullStr Protective role of small extracellular vesicles derived from HUVECs treated with AGEs in diabetic vascular calcification
title_full_unstemmed Protective role of small extracellular vesicles derived from HUVECs treated with AGEs in diabetic vascular calcification
title_short Protective role of small extracellular vesicles derived from HUVECs treated with AGEs in diabetic vascular calcification
title_sort protective role of small extracellular vesicles derived from huvecs treated with ages in diabetic vascular calcification
topic Vascular calcification
Diabetes
sEVs
miR-126-5p
Endothelial cells
url https://doi.org/10.1186/s12951-022-01529-z
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