过氧化物酶体增殖物激活受体γ促进外源性骨髓间充质干细胞表达Cx43的作用及机制 |
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作者姓名: | 晏 平 侯婧瑛 郑韶欣 龙会宝 周长青 郭天柱 伍权华 钟婷婷 王 彤 |
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作者单位: | 1广州医科大学附属第一医院急诊科,广东省广州市 510120
2中山大学孙逸仙纪念医院急诊科,广东省广州市 510120 |
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基金项目: | 国家自然科学基金(81270213)“ANGⅡ/AT1/SMAD/CX43通路在心肌干细胞提高心梗大鼠心电生理学稳定性和室颤阈值的作用机制研究”;国家自然科学基金(81070125)“抗凋亡与促血管生成miRNA-378干预MSCs治疗心梗后心衰的机制研究”;广东省科技计划项目(2010B031600032)“抗凋亡与促血管生成miRNA-378干预MSCs治疗心梗后心衰的机制研究”;高校基本科研业务费中山大学青年教师重点培育项目(13ykzd16) “PPAR-γ/TGF-β1/Smad/CX43通路在PPAR-γ干预MSCs治疗心梗后心衰的疗效及机制研究”;广东省科技计划项目(2014A020211002)“LncRNA-Bvht/MESP1/N-cadherin通路调控MSCs向心肌细胞定向分化的机制研究” |
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摘 要: |
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关 键 词: | 干细胞 骨髓干细胞 过氧化物酶体增殖物激活受体γ 骨髓间充质干细胞 心肌梗死 转化生长因子β1 缝隙连接蛋白43 国家自然科学基金 |
收稿时间: | 2016-04-19 |
Peroxisome proliferator-activated receptor gamma promotes exogenous mesenchymal stem cells to express connexin 43: its role and mechanism |
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Authors: | Yan Ping Hou Jing-ying Zheng Shao-xin Long Hui-bao Zhou Chang-qing Guo Tian-zhu Wu Quan-hua Zhong Ting-ting Wang Tong |
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Institution: | 1Department of Emergency, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, Guangdong Province, China
2Department of Emergency, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China |
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Abstract: | BACKGROUND:Piglitazone, a peroxisome proliferator-activated receptor γ (PPAR-γ) agonist, has been demonstrated to promote survival and cardiac differentiation of exogenous bone marrow mesenchymal stem cells to improve cardiac function. In this study, we attempted to investigate whether pioglitazone could induce cardiac differentiation of endogenous bone marrow mesenchymal stem cells and improve cardiac function, and meanwhile, probed into the relevant mechanisms.
OBJECTIVE:To compare the therapeutic efficacy of pioglitazone combined with bone marrow mesenchymal stem cell transplantation, pioglitazone alone and phosphate buffer solution (PBS) and to investigate the relevant mechanisms.
METHODS:Thirty Sprague-Dawley rats with myocardial infarction induced by ligation of the left anterior descending coronary artery were randomized into combined group (combination of bone marrow mesenchymal stem cells and pioglitazone), pioglitazone group and PBS group. Two weeks later, PKH26-labeled bone marrow mesenchymal stem cells in PBS or PBS alone were injected into the local infarct zone in the combined group and the other two groups, respectively. Pioglitazone (3 mg/kg/d) was given by the oral gavage in the combined and pioglitazone groups for continuous 2 weeks after cells transplantation. At 2 weeks after treatment, cardiac functions were evaluated. In addition, expressions of PPAR-γ, connexin 43 and relative factors in transforming growth factor-β1/SMAD signaling pathway were examined in different areas of the left ventricle from each harvested heart.
RESULTS AND CONCLUSION:There were no differences in the baseline parameters of cardiac function between the two groups. Two weeks after treatment, left ventricular end-diastolic diameter, left ventricular end-systolic diameter and left ventricular ejection fraction were significantly improved in the combined group compared with the other two groups; the expression of PPAR-γ was significantly increased in different zones of the left ventricle in the combined and pioglitazone groups. In the combined group, there was a significantly higher expression of connexin 43, and the levels of transforming growth factor-β1, SMAD2 and SMAD3 were obviously attenuated in the infarct and marginal zones. However, no differences were found in the above determinants between the pioglitazone and PBS groups. To conclude, pioglitazone cannot induce the differentiation and proliferation of endogenous bone marrow mesenchymal stem cells, but pioglitazone combined with exogenous bone marrow mesenchymal stem cells can improve cardiac function post myocardial infarction. In this process, PPAR-γ might promote the connexin 43 expression in exogenous bone marrow mesenchymal stem cells via the blockade of transforming growth factor-β1/SMAD signaling pathway. |
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Keywords: | Myocardial Infarction Peroxisome Proliferator-Activated Receptors Bone Marrow Mesenchymal Stem Cell Transplantation Transforming Growth Factor beta1 Connexins Tissue Engineering |
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