Peroxisome proliferator-activated receptor gamma promotes exogenous mesenchymal stem cells to express connexin 43: its role and mechanism

doi:10.3969/j.issn.2095-4344.2016.23.002

Abstract

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.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Myocardial Infarction, Peroxisome Proliferator-Activated Receptors, Bone Marrow, Mesenchymal Stem Cell Transplantation, Transforming Growth Factor beta1, Connexins, Tissue Engineering

CLC Number:

R394.2

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. Peroxisome proliferator-activated receptor gamma promotes exogenous mesenchymal stem cells to express connexin 43: its role and mechanism[J]. Chinese Journal of Tissue Engineering Research, 2016, 20(23): 3357-3365.

Figures/Tables 4

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