Ren Mingming, Wang Tao, Huang Lei, Ye Xiaoqiang, Xv Zhifeng, Ouyang Chun, Han Zhen
Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong Province, China.
Cardiovasc Ther. 2016 Dec;34(6):482-488. doi: 10.1111/1755-5922.12228.
Accumulating evidence showed that transient receptor potential channels play an important role in the regulation of cardiomyocyte differentiation. The vanilloid receptor 1 (VR1) is a member of the transient receptor channel super family and is expressed in cardiomyocytes. However, its function in cardiomyocytes remains unclear.
Herein, the aim of this study was to investigate the functional role of VR1 in the cardiomyocyte differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) and to elucidate the potential molecular mechanisms.
Immunofluorescence assay showed that cardiomyocyte marker cardiac troponin T (cTnT) was found significantly elevated in differentiated BMSCs induced by 5-azacytidine compared with control. Similarly, VR1 expression was also found significantly increased in induced BMSCs differentiation. Additionally, we examined the role of VR1 in BMSC differentiation processes through VR1 siRNAs. We found that the expression of cardiomyocyte marker genes, such as alpha-myosin heavy chain (α-MHC), α-cardiac actin, and Nkx2.5 (cardiac-specific transcription factor), was significantly decreased when VR1 was silenced. Furthermore, we found that inhibition of VR1 expression is associated with downregulation of Wnt/β-catenin signaling.
To summarize, our data demonstrate important role of VR1 in BMSCs differentiation into cardiomyocytes in conjunction of Wnt/β-catenin signaling.
越来越多的证据表明,瞬时受体电位通道在心肌细胞分化的调节中起重要作用。香草酸受体1(VR1)是瞬时受体通道超家族的成员,在心肌细胞中表达。然而,其在心肌细胞中的功能仍不清楚。
在此,本研究的目的是探讨VR1在骨髓间充质干细胞(BMSC)向心肌细胞分化中的功能作用,并阐明潜在的分子机制。
免疫荧光分析显示,与对照组相比,5-氮杂胞苷诱导分化的BMSC中心肌细胞标志物心肌肌钙蛋白T(cTnT)显著升高。同样,在诱导的BMSC分化中也发现VR1表达显著增加。此外,我们通过VR1小干扰RNA研究了VR1在BMSC分化过程中的作用。我们发现,当VR1沉默时,心肌细胞标志物基因如α-肌球蛋白重链(α-MHC)、α-心肌肌动蛋白和Nkx2.5(心脏特异性转录因子)的表达显著降低。此外,我们发现VR1表达的抑制与Wnt/β-连环蛋白信号通路的下调有关。
总之,我们的数据表明VR1在Wnt/β-连环蛋白信号通路的协同作用下,在BMSC向心肌细胞的分化中起重要作用。