Role of VR1 in the differentiation of bone marrow-derived mesenchymal stem cells into cardiomyocytes associated with Wnt/β-catenin signaling.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
To summarize, our data demonstrate important role of VR1 in BMSCs differentiation into cardiomyocytes in conjunction of Wnt/β-catenin signaling.
Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong Province, China.
Mingming
M
Ren
Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong Province, China.
Tao
T
Wang
Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong Province, China.
Lei
L
Huang
Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong Province, China.
Xiaoqiang
X
Ye
Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong Province, China.
Zhifeng
Z
Xv
Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong Province, China.
Chun
C
Ouyang
Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong Province, China.
Zhen
Z
Han
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D001374:Azacitidine / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D017207:Rats, Sprague-Dawley; D050916:TRPV Cation Channels / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D020107:Troponin T / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects; D051176:beta Catenin / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C572053:Axin2 protein, rat; D002352:Carrier Proteins; C495268:Ctnnb1 protein, rat; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D020107:Troponin T; D051176:beta Catenin; D001374:Azacitidine
Bone marrow-derived mesenchymal stem cells; Cardiomyocytes; Differentiation; Vanilloid receptor 1