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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Dove Medical Press
2021
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oai:doaj.org-article:77ca4352fe79411297dd5c667a89538a2021-12-02T14:02:58ZMesenchymal Stem Cell-Derived Exosomes Carry MicroRNA-125a to Protect Against Diabetic Nephropathy by Targeting Histone Deacetylase 1 and Downregulating Endothelin-11178-7007https://doaj.org/article/77ca4352fe79411297dd5c667a89538a2021-03-01T00:00:00Zhttps://www.dovepress.com/mesenchymal-stem-cell-derived-exosomes-carry-microrna-125a-to-protect--peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Yan 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 nephropathyHao YMiao JLiu WCai KHuang XPeng LDove Medical Pressarticleexosomesmir-125ahdac1et-1diabetic nephropathySpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 14, Pp 1405-1418 (2021) |
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exosomes mir-125a hdac1 et-1 diabetic nephropathy Specialties of internal medicine RC581-951 |
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exosomes mir-125a hdac1 et-1 diabetic nephropathy Specialties of internal medicine RC581-951 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 |
| 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 |
| format |
article |
| author |
Hao Y Miao J Liu W Cai K Huang X Peng L |
| 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 |
| publishDate |
2021 |
| url |
https://doaj.org/article/77ca4352fe79411297dd5c667a89538a |
| work_keys_str_mv |
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| _version_ |
1718392089140527104 |