Cargando…
Hyperglycaemia-induced reciprocal changes in miR-30c and PAI-1 expression in platelets
Type 2 diabetic mellitus (DM2) is associated with accelerated thrombotic complications and is characterized by high levels of plasminogen activator inhibitor-1 (PAI-1). Recent studies show that human platelets have high levels of miR-30c and synthesize considerable active PAI-1. The underlying mecha...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5098184/ https://www.ncbi.nlm.nih.gov/pubmed/27819307 http://dx.doi.org/10.1038/srep36687 |
_version_ | 1782465735074775040 |
---|---|
author | Luo, Mao Li, Rong Ren, Meiping Chen, Ni Deng, Xin Tan, Xiaoyong Li, Yongjie Zeng, Min Yang, Yan Wan, Qin Wu, Jianbo |
author_facet | Luo, Mao Li, Rong Ren, Meiping Chen, Ni Deng, Xin Tan, Xiaoyong Li, Yongjie Zeng, Min Yang, Yan Wan, Qin Wu, Jianbo |
author_sort | Luo, Mao |
collection | PubMed |
description | Type 2 diabetic mellitus (DM2) is associated with accelerated thrombotic complications and is characterized by high levels of plasminogen activator inhibitor-1 (PAI-1). Recent studies show that human platelets have high levels of miR-30c and synthesize considerable active PAI-1. The underlying mechanism of how PAI-1 expression is upregulated in DM2 is poorly understood. We now report that hyperglycaemia-induced repression of miR-30c increases PAI-1 expression and thrombus formation in DM2. Bioinformatic analysis and identification of miRNA targets were assessed using luciferase assays, quantitative real-time PCR and western blots in vitro and in vivo. The changes in miR-30c and PAI-1 levels were identified in platelets from healthy and diabetic individuals. We found that miR-30c directly targeted the 3′ UTR of PAI-1 and negatively regulated its expression. miR-30c was negatively correlated with glucose and HbA1c levels in DM2. In HFD-fed diabetic mice, increasing miR-30c expression by lenti-miR-30c significantly decreased the PAI-1 expression and prolonged the time to occlusion in an arterial thrombosis model. Platelet depletion/reinfusion experiments generating mice with selective ablation of PAI-1 demonstrate a major contribution by platelet-derived PAI-1 in the treatment of lenti-miR-30c to thrombus formation. These results provide important implications regarding the regulation of fibrinolysis by platelet miRNA under diabetic mellitus. |
format | Online Article Text |
id | pubmed-5098184 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-50981842016-11-10 Hyperglycaemia-induced reciprocal changes in miR-30c and PAI-1 expression in platelets Luo, Mao Li, Rong Ren, Meiping Chen, Ni Deng, Xin Tan, Xiaoyong Li, Yongjie Zeng, Min Yang, Yan Wan, Qin Wu, Jianbo Sci Rep Article Type 2 diabetic mellitus (DM2) is associated with accelerated thrombotic complications and is characterized by high levels of plasminogen activator inhibitor-1 (PAI-1). Recent studies show that human platelets have high levels of miR-30c and synthesize considerable active PAI-1. The underlying mechanism of how PAI-1 expression is upregulated in DM2 is poorly understood. We now report that hyperglycaemia-induced repression of miR-30c increases PAI-1 expression and thrombus formation in DM2. Bioinformatic analysis and identification of miRNA targets were assessed using luciferase assays, quantitative real-time PCR and western blots in vitro and in vivo. The changes in miR-30c and PAI-1 levels were identified in platelets from healthy and diabetic individuals. We found that miR-30c directly targeted the 3′ UTR of PAI-1 and negatively regulated its expression. miR-30c was negatively correlated with glucose and HbA1c levels in DM2. In HFD-fed diabetic mice, increasing miR-30c expression by lenti-miR-30c significantly decreased the PAI-1 expression and prolonged the time to occlusion in an arterial thrombosis model. Platelet depletion/reinfusion experiments generating mice with selective ablation of PAI-1 demonstrate a major contribution by platelet-derived PAI-1 in the treatment of lenti-miR-30c to thrombus formation. These results provide important implications regarding the regulation of fibrinolysis by platelet miRNA under diabetic mellitus. Nature Publishing Group 2016-11-07 /pmc/articles/PMC5098184/ /pubmed/27819307 http://dx.doi.org/10.1038/srep36687 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Luo, Mao Li, Rong Ren, Meiping Chen, Ni Deng, Xin Tan, Xiaoyong Li, Yongjie Zeng, Min Yang, Yan Wan, Qin Wu, Jianbo Hyperglycaemia-induced reciprocal changes in miR-30c and PAI-1 expression in platelets |
title | Hyperglycaemia-induced reciprocal changes in miR-30c and PAI-1 expression in platelets |
title_full | Hyperglycaemia-induced reciprocal changes in miR-30c and PAI-1 expression in platelets |
title_fullStr | Hyperglycaemia-induced reciprocal changes in miR-30c and PAI-1 expression in platelets |
title_full_unstemmed | Hyperglycaemia-induced reciprocal changes in miR-30c and PAI-1 expression in platelets |
title_short | Hyperglycaemia-induced reciprocal changes in miR-30c and PAI-1 expression in platelets |
title_sort | hyperglycaemia-induced reciprocal changes in mir-30c and pai-1 expression in platelets |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5098184/ https://www.ncbi.nlm.nih.gov/pubmed/27819307 http://dx.doi.org/10.1038/srep36687 |
work_keys_str_mv | AT luomao hyperglycaemiainducedreciprocalchangesinmir30candpai1expressioninplatelets AT lirong hyperglycaemiainducedreciprocalchangesinmir30candpai1expressioninplatelets AT renmeiping hyperglycaemiainducedreciprocalchangesinmir30candpai1expressioninplatelets AT chenni hyperglycaemiainducedreciprocalchangesinmir30candpai1expressioninplatelets AT dengxin hyperglycaemiainducedreciprocalchangesinmir30candpai1expressioninplatelets AT tanxiaoyong hyperglycaemiainducedreciprocalchangesinmir30candpai1expressioninplatelets AT liyongjie hyperglycaemiainducedreciprocalchangesinmir30candpai1expressioninplatelets AT zengmin hyperglycaemiainducedreciprocalchangesinmir30candpai1expressioninplatelets AT yangyan hyperglycaemiainducedreciprocalchangesinmir30candpai1expressioninplatelets AT wanqin hyperglycaemiainducedreciprocalchangesinmir30candpai1expressioninplatelets AT wujianbo hyperglycaemiainducedreciprocalchangesinmir30candpai1expressioninplatelets |