Adiponectin Modified BMSCs Alleviate Heart Fibrosis via Inhibition TGF-beta1/Smad in Diabetic Rats
Background: Accumulating evidence suggested that bone marrow mesenchymal stem cells (BMSCs) have therapeutic potential for diabetes and heart diseases. However, the effects of BMSC on reducing myocardial fibrosis need to be optimized. This study aimed to investigate the mechanism of adiponectin (APN...
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doaj-5d13e0a99efa4dd38ca375d36650016d2021-03-22T05:22:21ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-03-01910.3389/fcell.2021.644160644160Adiponectin Modified BMSCs Alleviate Heart Fibrosis via Inhibition TGF-beta1/Smad in Diabetic RatsKe Meng0Ke Meng1Huabo Cai2Simin Cai3Simin Cai4Yucai Hong5Xiaoming Zhang6Xiaoming Zhang7Department of Anatomy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Emergency Medicine, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Emergency Medicine, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Anatomy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Emergency Medicine, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Emergency Medicine, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Anatomy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaDepartment of Emergency Medicine, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaBackground: Accumulating evidence suggested that bone marrow mesenchymal stem cells (BMSCs) have therapeutic potential for diabetes and heart diseases. However, the effects of BMSC on reducing myocardial fibrosis need to be optimized. This study aimed to investigate the mechanism of adiponectin (APN) modified BMSCs on myocardial fibrosis in diabetic model in vivo and in vitro.Methods: The high-fat diet combined with streptozotocin (STZ) injection were used to induced diabetic rat model. H9c2 cells were cultured under a high glucose medium as in vitro model. The BMSCs were modified by APN plasmid or APN small interfering RNA (siRNA), then transplanted to the diabetic rats by a single tail-vein injection, or co-cultured with H9c2 cells.Results: We demonstrated that diabetic rats showed typical diabetic symptoms, such as decreased cardiac function, accumulation of pathological lesions and collagen expression. However, these impairments were significantly prevented by the APN modified BMSCs treatment while no effects on APN siRNA modified BMSCs treated diabetic rats. Moreover, we confirmed that APN modified BMSCs could attenuate the expression of TGF-beta1/smad to suppress the myocardial fibrosis in the diabetic rats and high glucose induced H9c2 cells.Conclusion: The present results for the first time showed that APN modified BMSCs exerted protection on cardiac fibrosis via inhibiting TGF-beta1/smad signal pathway in diabetic rats. Our findings suggested that APN modified BMSCs might be a novel and optimal therapy for the diabetic cardiomyopathy in future.https://www.frontiersin.org/articles/10.3389/fcell.2021.644160/fulldiabetic cardiomyopathyadiponectinbone marrow mesenchymal stem cellsTGF-beta1myocardial fibrosis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ke Meng Ke Meng Huabo Cai Simin Cai Simin Cai Yucai Hong Xiaoming Zhang Xiaoming Zhang |
spellingShingle |
Ke Meng Ke Meng Huabo Cai Simin Cai Simin Cai Yucai Hong Xiaoming Zhang Xiaoming Zhang Adiponectin Modified BMSCs Alleviate Heart Fibrosis via Inhibition TGF-beta1/Smad in Diabetic Rats Frontiers in Cell and Developmental Biology diabetic cardiomyopathy adiponectin bone marrow mesenchymal stem cells TGF-beta1 myocardial fibrosis |
author_facet |
Ke Meng Ke Meng Huabo Cai Simin Cai Simin Cai Yucai Hong Xiaoming Zhang Xiaoming Zhang |
author_sort |
Ke Meng |
title |
Adiponectin Modified BMSCs Alleviate Heart Fibrosis via Inhibition TGF-beta1/Smad in Diabetic Rats |
title_short |
Adiponectin Modified BMSCs Alleviate Heart Fibrosis via Inhibition TGF-beta1/Smad in Diabetic Rats |
title_full |
Adiponectin Modified BMSCs Alleviate Heart Fibrosis via Inhibition TGF-beta1/Smad in Diabetic Rats |
title_fullStr |
Adiponectin Modified BMSCs Alleviate Heart Fibrosis via Inhibition TGF-beta1/Smad in Diabetic Rats |
title_full_unstemmed |
Adiponectin Modified BMSCs Alleviate Heart Fibrosis via Inhibition TGF-beta1/Smad in Diabetic Rats |
title_sort |
adiponectin modified bmscs alleviate heart fibrosis via inhibition tgf-beta1/smad in diabetic rats |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cell and Developmental Biology |
issn |
2296-634X |
publishDate |
2021-03-01 |
description |
Background: Accumulating evidence suggested that bone marrow mesenchymal stem cells (BMSCs) have therapeutic potential for diabetes and heart diseases. However, the effects of BMSC on reducing myocardial fibrosis need to be optimized. This study aimed to investigate the mechanism of adiponectin (APN) modified BMSCs on myocardial fibrosis in diabetic model in vivo and in vitro.Methods: The high-fat diet combined with streptozotocin (STZ) injection were used to induced diabetic rat model. H9c2 cells were cultured under a high glucose medium as in vitro model. The BMSCs were modified by APN plasmid or APN small interfering RNA (siRNA), then transplanted to the diabetic rats by a single tail-vein injection, or co-cultured with H9c2 cells.Results: We demonstrated that diabetic rats showed typical diabetic symptoms, such as decreased cardiac function, accumulation of pathological lesions and collagen expression. However, these impairments were significantly prevented by the APN modified BMSCs treatment while no effects on APN siRNA modified BMSCs treated diabetic rats. Moreover, we confirmed that APN modified BMSCs could attenuate the expression of TGF-beta1/smad to suppress the myocardial fibrosis in the diabetic rats and high glucose induced H9c2 cells.Conclusion: The present results for the first time showed that APN modified BMSCs exerted protection on cardiac fibrosis via inhibiting TGF-beta1/smad signal pathway in diabetic rats. Our findings suggested that APN modified BMSCs might be a novel and optimal therapy for the diabetic cardiomyopathy in future. |
topic |
diabetic cardiomyopathy adiponectin bone marrow mesenchymal stem cells TGF-beta1 myocardial fibrosis |
url |
https://www.frontiersin.org/articles/10.3389/fcell.2021.644160/full |
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