Hyperglycemia Altered the Fate of Cardiac Stem Cells to Adipogenesis through Inhibiting the β-Catenin/TCF-4 Pathway
Hyperglycemia Altered the Fate of Cardiac Stem Cells to Adipogenesis through Inhibiting the β-Catenin/TCF-4 Pathway
复制标题
高血糖通过抑制 β-Catenin/TCF-4 途径改变心脏干细胞脂肪生成的命运
DOI：
10.1159/000493828
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发表时间：
2018-09
期刊：
影响因子：
--
通讯作者：
zhang x
中科院分区：
文献类型：
--
作者：
zhang x
背景/目的：高血糖是糖尿病患者最严重心血管疾病的重要危险因素。已有研究表明，心脏干细胞(CSCs)在维持心脏内环境稳定和再生方面起着关键作用。然而，糖尿病对CSCs影响的潜在机制仍不清楚。本研究表明，高血糖可能促进CSCs的脂肪生成，从而导致糖尿病患者心肌再生能力下降。方法：分离培养CSCs，在高糖条件下培养。免疫荧光染色和免疫印迹法检测β-catenin和Tcf-4的表达水平。成脂诱导后，用流式细胞仪和免疫印迹法检测成脂转录因子和CSCs标志物的表达。此外，油红O染色用于研究在有或没有氯化锂诱导脂肪形成的过程中脂滴的形成。氯化锂是一种有效的Tcf/β-连环蛋白依赖转录的激活剂。结果：高糖条件抑制了β-连环蛋白/TCF4的核转位，促进了成脂作用。诱导成脂后，高糖组CSCs成脂转录因子(PPARγ、ADD1、C/EBPα)表达增加(P<0.01)，CSCs标志物c-Kit、Sca-1、MDR-1、ISL-1表达降低(P<；0.01)。此外，在高糖培养的CSCs中，脂滴的形成增加，而LiCl抑制这些CSCs的脂滴形成(P<；0.01)。结论：高血糖抑制β-catenin/Tcf-4通路，促进CSCs成脂。我们的发现为未来糖尿病患者异常心肌再生和心外膜脂肪的介入治疗提供了新的机会。
Background/Aims: Hyperglycemia is an important risk factor for the most severe cardiovascular diseases in patients with diabetes. It has been demonstrated that cardiac stem cells (CSCs) play a pivotal role in the maintenance of cardiac homeostasis and regeneration. However, the mechanism underlying the influence of diabetes on CSCs remains unclear. This study demonstrated that hyperglycemia might promote adipogenesis in CSCs, which induces a decline in myocardial regeneration capability in diabetes. Methods: CSCs were isolated and cultured in high-glucose medium. The levels of β-catenin and TCF-4 in CSCs were determined by immunofluorescence staining and western blot analysis. Adipogenic transcriptional factors and CSCs markers were also examined by flow cytometry and western blot analysis after adipogenesis induction. In addition, Oil Red O staining was performed to investigate lipid droplet formation during adipogenesis induction with or without LiCl, a potent activator of TCF/β-catenin-dependent transcription. Results: High-glucose conditions inhibited nuclear translocation of β-catenin/TCF-4 and promoted adipogenesis in CSCs. After adipogenesis induction, expression of adipogenic transcriptional factors (PPARγ, ADD1, and C/EBPα) were increased (P < 0.01) and that of CSCs markers (c-Kit, Sca-1, MDR-1, and isl-1) were decreased (P< 0.01) in CSCs in the high-glucose group. Furthermore, lipid droplet formation was increased in CSCs cultured with high glucose, while LiCl attenuated lipid droplet formation in these CSCs (P < 0.01). Conclusion: These results demonstrated that hyperglycemia inhibited the β-catenin/TCF-4 pathway and promoted CSCs adipogenesis. Our findings suggest a new opportunity for future interventional strategie for abnormal myocardial regeneration and epicardial fat in patients with diabetes.
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影响因子：
64.5
作者：
Ellison, Georgina M.;Vicinanza, Carla;Nadal-Ginard, Bernardo
通讯作者：
Nadal-Ginard, Bernardo
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影响因子：
3.5
作者：
Liu Wei;Pu Yujie;Wang Chao;Gu Chuanlong;Zhang Xiaoming
通讯作者：
Zhang Xiaoming
DOI：
--
发表时间：
--
期刊：
--
影响因子：
--
作者：
Biochemistr;Biochemistr And Biochemistry;Ying-kui Yang;Min Chen;R. Clements;G. Abrams;C. Aprahamian;C. Harmon
通讯作者：
Biochemistr;Biochemistr And Biochemistry;Ying-kui Yang;Min Chen;R. Clements;G. Abrams;C. Aprahamian;C. Harmon
影响因子：
3.5
作者：
Gianfranceschi, Giuseppe;Caragnano, Angela;Beltrami, Antonio Paolo
通讯作者：
Beltrami, Antonio Paolo
DOI：
10.1074/jbc.m115.641332
发表时间：
2015-06
期刊：
The Journal of Biological Chemistry
影响因子：
--
作者：
Li Wang;L. Di
通讯作者：
Li Wang;L. Di