Metformin Inhibits the Expression of Biomarkers of Fibrosis of EPCs In Vitro

Endothelial progenitor cells (EPCs) are a group of circulating cells with important functions in vascular repair and treatment of cardiovascular diseases. However, in patients with atrial fibrillation (AF), the number and function of EPCs reportedly are decreased. TGF-β is highly expressed in AF pat...

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Main Authors: Fei Han, Jie Shu, Shunjun Wang, Can-e Tang, Fanyan Luo
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2019/9019648
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author Fei Han
Jie Shu
Shunjun Wang
Can-e Tang
Fanyan Luo
author_facet Fei Han
Jie Shu
Shunjun Wang
Can-e Tang
Fanyan Luo
author_sort Fei Han
collection DOAJ
description Endothelial progenitor cells (EPCs) are a group of circulating cells with important functions in vascular repair and treatment of cardiovascular diseases. However, in patients with atrial fibrillation (AF), the number and function of EPCs reportedly are decreased. TGF-β is highly expressed in AF patients. In this study, we examined the effect of TGF-β1 on EPCs and the therapeutic outcome of metformin treatment on TGF-β1-induced EPCs. EPCs were induced with TGF-β1 at different concentrations (5 ng/ml, 10 ng/ml, and 20 ng/ml) for 48 h followed by western blot, qPCR, and immunofluorescence analyses to investigate changes in the levels of the fibrosis-related proteins, α-SMA, Col I, Col III, CTGF, and MMP-1. Live-dead cell staining was used to evaluate cell apoptosis. Compared with the control, TGF-β1 treatment significantly (p<0.05) enhanced the levels of α-SMA, Col I, Col III, CTGF, and MMP-1 in a dose-dependent manner. The most effective concentration of TGF-β1 (20 ng/ml) was then used to induce fibrosis biomarker expression in EPCs, followed by treatment with metformin at different concentrations (0.5, 1, and 2 mmol/l). Metformin treatment suppressed TGF-β-induced expression of all above factors, with the effect at 2 mmol/l being significant (p<0.05). Live-dead cell staining showed no difference among the control, TGF-β1-treated, and metformin-treated groups. In conclusion, our study showed that TGF-β1 induces the expression of fibrosis biomarkers in EPCs, which is attenuated by treatment with metformin. Thus, metformin may have therapeutic potential for improving EPC function in cardiovascular diseases.
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spelling doaj-art-00fc0cb582914c62b4b3ad0609d353ad2025-08-20T03:22:33ZengWileyStem Cells International1687-966X1687-96782019-01-01201910.1155/2019/90196489019648Metformin Inhibits the Expression of Biomarkers of Fibrosis of EPCs In VitroFei Han0Jie Shu1Shunjun Wang2Can-e Tang3Fanyan Luo4Department of Cardiothoracic Surgery, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, ChinaDepartment of Cardiothoracic Surgery, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, ChinaDepartment of Cardiothoracic Surgery, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, ChinaThe Institute of Medical Science Research, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, ChinaDepartment of Cardiothoracic Surgery, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, ChinaEndothelial progenitor cells (EPCs) are a group of circulating cells with important functions in vascular repair and treatment of cardiovascular diseases. However, in patients with atrial fibrillation (AF), the number and function of EPCs reportedly are decreased. TGF-β is highly expressed in AF patients. In this study, we examined the effect of TGF-β1 on EPCs and the therapeutic outcome of metformin treatment on TGF-β1-induced EPCs. EPCs were induced with TGF-β1 at different concentrations (5 ng/ml, 10 ng/ml, and 20 ng/ml) for 48 h followed by western blot, qPCR, and immunofluorescence analyses to investigate changes in the levels of the fibrosis-related proteins, α-SMA, Col I, Col III, CTGF, and MMP-1. Live-dead cell staining was used to evaluate cell apoptosis. Compared with the control, TGF-β1 treatment significantly (p<0.05) enhanced the levels of α-SMA, Col I, Col III, CTGF, and MMP-1 in a dose-dependent manner. The most effective concentration of TGF-β1 (20 ng/ml) was then used to induce fibrosis biomarker expression in EPCs, followed by treatment with metformin at different concentrations (0.5, 1, and 2 mmol/l). Metformin treatment suppressed TGF-β-induced expression of all above factors, with the effect at 2 mmol/l being significant (p<0.05). Live-dead cell staining showed no difference among the control, TGF-β1-treated, and metformin-treated groups. In conclusion, our study showed that TGF-β1 induces the expression of fibrosis biomarkers in EPCs, which is attenuated by treatment with metformin. Thus, metformin may have therapeutic potential for improving EPC function in cardiovascular diseases.http://dx.doi.org/10.1155/2019/9019648
spellingShingle Fei Han
Jie Shu
Shunjun Wang
Can-e Tang
Fanyan Luo
Metformin Inhibits the Expression of Biomarkers of Fibrosis of EPCs In Vitro
Stem Cells International
title Metformin Inhibits the Expression of Biomarkers of Fibrosis of EPCs In Vitro
title_full Metformin Inhibits the Expression of Biomarkers of Fibrosis of EPCs In Vitro
title_fullStr Metformin Inhibits the Expression of Biomarkers of Fibrosis of EPCs In Vitro
title_full_unstemmed Metformin Inhibits the Expression of Biomarkers of Fibrosis of EPCs In Vitro
title_short Metformin Inhibits the Expression of Biomarkers of Fibrosis of EPCs In Vitro
title_sort metformin inhibits the expression of biomarkers of fibrosis of epcs in vitro
url http://dx.doi.org/10.1155/2019/9019648
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