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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BMC
2022-07-01
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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 |
first_indexed | 2024-04-14T00:22:06Z |
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id | doaj.art-bdc96960b2c742299c5a6a748d9e530f |
institution | Directory Open Access Journal |
issn | 1477-3155 |
language | English |
last_indexed | 2024-04-14T00:22:06Z |
publishDate | 2022-07-01 |
publisher | BMC |
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series | Journal of Nanobiotechnology |
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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