Mesenchymal Stem Cell-Derived Exosomes Carry MicroRNA-125a to Protect Against Diabetic Nephropathy by Targeting Histone Deacetylase 1 and Downregulating Endothelin-1
Yan Hao,1 Jie Miao,2 Wenjia Liu,1 Kangqin Cai,1 Xianli Huang,1 Li Peng1 1Department of Nephrology, The First People’s Hospital of Zigong, Zigong, 643000, Sichuan, People’s Republic of China; 2Department of Nephrology, The Health and Rehabilitation Vocational College of Sichuan, Z...
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doaj-77ca4352fe79411297dd5c667a89538a2021-03-28T19:57:50ZengDove Medical PressDiabetes, Metabolic Syndrome and Obesity : Targets and Therapy1178-70072021-03-01Volume 141405141863427Mesenchymal Stem Cell-Derived Exosomes Carry MicroRNA-125a to Protect Against Diabetic Nephropathy by Targeting Histone Deacetylase 1 and Downregulating Endothelin-1Hao YMiao JLiu WCai KHuang XPeng LYan Hao,1 Jie Miao,2 Wenjia Liu,1 Kangqin Cai,1 Xianli Huang,1 Li Peng1 1Department of Nephrology, The First People’s Hospital of Zigong, Zigong, 643000, Sichuan, People’s Republic of China; 2Department of Nephrology, The Health and Rehabilitation Vocational College of Sichuan, Zigong, 643000, Sichuan, People’s Republic of ChinaCorrespondence: Yan HaoDepartment of Nephrology, The First People’s Hospital of Zigong, No. 42, Shangyi Road, Daoshenghao Community, Ziliujing District, Zigong, 643000, Sichuan, People’s Republic of ChinaTel/Fax +86-13990087106Email haoyan12301@163.comBackground: Mesenchymal stem cell (MSC)-derived exosomes have seen great advances in human disease control in a minimally invasive manner. This research aimed to explore the function of MSC-derived exosomes in diabetic nephropathy (DN) progression and the molecules involved.Methods: A rat model with DN and rat glomerular mesangial cell (GMC) models treated with high glucose (HG) were established, which were treated with exosomes from adipose-derived-MSCs (adMSCs). The levels of blood glucose, serum creatinine, and urinary protein, the urine albumin-to-creatinine ratio (UACR), kidney weight/body weight, and mesangial hyperplasia and kidney fibrosis in rats were determined. The expression of interleukin-6 (IL-6), collagen I (Col. I), fibronectin (FN), Bax and Bcl-2 in HG-treated GMCs was assessed. The microRNA (miRNA) carried by adMSC-exosomes was identified, and the implicated down-stream molecules were analyzed.Results: adMSC-derived exosomes decreased levels of blood glucose, serum creatinine, 24-h urinary protein, UACR and kidney weight/body weight, and they suppressed mesangial hyperplasia and kidney fibrosis in DN rats. The exosomes also suppressed levels of IL6, Col. I and FN in HG-treated GMCs and promoted cell apoptosis. miR-125a was at least partially responsible for the above protective events mediated by adMSC-exosomes. miR-125a directly bound to histone deacetylase 1 (HDAC1), while HDAC1 further regulated endothelin-1 (ET-1) activation. Up-regulation of HDAC1 blocked the functions of adMSC-exosomal miR-125a.Conclusion: This study suggested that adMSC-derived exosomes inhibit DN progression and alleviate the symptoms by carrying miR-125a, during which HDAC1 and ET-1 were inhibited. This study may provide novel effects into DN treatment.Keywords: exosomes, miR-125a, HDAC1, ET-1, diabetic nephropathyhttps://www.dovepress.com/mesenchymal-stem-cell-derived-exosomes-carry-microrna-125a-to-protect--peer-reviewed-article-DMSOexosomesmir-125ahdac1et-1diabetic nephropathy |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hao Y Miao J Liu W Cai K Huang X Peng L |
spellingShingle |
Hao Y Miao J Liu W Cai K Huang X Peng L Mesenchymal Stem Cell-Derived Exosomes Carry MicroRNA-125a to Protect Against Diabetic Nephropathy by Targeting Histone Deacetylase 1 and Downregulating Endothelin-1 Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy exosomes mir-125a hdac1 et-1 diabetic nephropathy |
author_facet |
Hao Y Miao J Liu W Cai K Huang X Peng L |
author_sort |
Hao Y |
title |
Mesenchymal Stem Cell-Derived Exosomes Carry MicroRNA-125a to Protect Against Diabetic Nephropathy by Targeting Histone Deacetylase 1 and Downregulating Endothelin-1 |
title_short |
Mesenchymal Stem Cell-Derived Exosomes Carry MicroRNA-125a to Protect Against Diabetic Nephropathy by Targeting Histone Deacetylase 1 and Downregulating Endothelin-1 |
title_full |
Mesenchymal Stem Cell-Derived Exosomes Carry MicroRNA-125a to Protect Against Diabetic Nephropathy by Targeting Histone Deacetylase 1 and Downregulating Endothelin-1 |
title_fullStr |
Mesenchymal Stem Cell-Derived Exosomes Carry MicroRNA-125a to Protect Against Diabetic Nephropathy by Targeting Histone Deacetylase 1 and Downregulating Endothelin-1 |
title_full_unstemmed |
Mesenchymal Stem Cell-Derived Exosomes Carry MicroRNA-125a to Protect Against Diabetic Nephropathy by Targeting Histone Deacetylase 1 and Downregulating Endothelin-1 |
title_sort |
mesenchymal stem cell-derived exosomes carry microrna-125a to protect against diabetic nephropathy by targeting histone deacetylase 1 and downregulating endothelin-1 |
publisher |
Dove Medical Press |
series |
Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy |
issn |
1178-7007 |
publishDate |
2021-03-01 |
description |
Yan Hao,1 Jie Miao,2 Wenjia Liu,1 Kangqin Cai,1 Xianli Huang,1 Li Peng1 1Department of Nephrology, The First People’s Hospital of Zigong, Zigong, 643000, Sichuan, People’s Republic of China; 2Department of Nephrology, The Health and Rehabilitation Vocational College of Sichuan, Zigong, 643000, Sichuan, People’s Republic of ChinaCorrespondence: Yan HaoDepartment of Nephrology, The First People’s Hospital of Zigong, No. 42, Shangyi Road, Daoshenghao Community, Ziliujing District, Zigong, 643000, Sichuan, People’s Republic of ChinaTel/Fax +86-13990087106Email haoyan12301@163.comBackground: Mesenchymal stem cell (MSC)-derived exosomes have seen great advances in human disease control in a minimally invasive manner. This research aimed to explore the function of MSC-derived exosomes in diabetic nephropathy (DN) progression and the molecules involved.Methods: A rat model with DN and rat glomerular mesangial cell (GMC) models treated with high glucose (HG) were established, which were treated with exosomes from adipose-derived-MSCs (adMSCs). The levels of blood glucose, serum creatinine, and urinary protein, the urine albumin-to-creatinine ratio (UACR), kidney weight/body weight, and mesangial hyperplasia and kidney fibrosis in rats were determined. The expression of interleukin-6 (IL-6), collagen I (Col. I), fibronectin (FN), Bax and Bcl-2 in HG-treated GMCs was assessed. The microRNA (miRNA) carried by adMSC-exosomes was identified, and the implicated down-stream molecules were analyzed.Results: adMSC-derived exosomes decreased levels of blood glucose, serum creatinine, 24-h urinary protein, UACR and kidney weight/body weight, and they suppressed mesangial hyperplasia and kidney fibrosis in DN rats. The exosomes also suppressed levels of IL6, Col. I and FN in HG-treated GMCs and promoted cell apoptosis. miR-125a was at least partially responsible for the above protective events mediated by adMSC-exosomes. miR-125a directly bound to histone deacetylase 1 (HDAC1), while HDAC1 further regulated endothelin-1 (ET-1) activation. Up-regulation of HDAC1 blocked the functions of adMSC-exosomal miR-125a.Conclusion: This study suggested that adMSC-derived exosomes inhibit DN progression and alleviate the symptoms by carrying miR-125a, during which HDAC1 and ET-1 were inhibited. This study may provide novel effects into DN treatment.Keywords: exosomes, miR-125a, HDAC1, ET-1, diabetic nephropathy |
topic |
exosomes mir-125a hdac1 et-1 diabetic nephropathy |
url |
https://www.dovepress.com/mesenchymal-stem-cell-derived-exosomes-carry-microrna-125a-to-protect--peer-reviewed-article-DMSO |
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