Activation of TRPV2 negatively regulates the differentiation of mouse brown adipocytes
Activation of TRPV2 negatively regulates the differentiation of mouse brown adipocytes
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DOI：
10.1007/s00424-016-1846-1
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发表时间：
2016-06
期刊：
影响因子：
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通讯作者：
Wuping Sun;K. Uchida;N. Takahashi;Y. Iwata;S. Wakabayashi;T. Goto;T. Kawada;M. Tominaga
中科院分区：
文献类型：
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作者：
Wuping Sun;K. Uchida;N. Takahashi;Y. Iwata;S. Wakabayashi;T. Goto;T. Kawada;M. Tominaga
瞬时受体电位香草蛋白2 （TRPV2）作为Ca2+渗透性非选择性阳离子通道，据报道对温度、机械力和一些化学物质敏感。我们最近发现TRPV2对于维持小鼠棕色脂肪组织的产热功能至关重要。然而，TRPV2在棕色脂肪细胞分化中的作用尚不清楚。我们发现TRPV2的表达在棕色脂肪细胞的分化过程中显著增加。非选择性TRPV2激动剂（2-氨基乙氧基二苯硼酸酯和溶血磷脂酰胆碱）在棕色脂肪细胞分化早期以剂量依赖性方式抑制棕色脂肪细胞的分化。trpv2选择性拮抗剂SKF96365 （SKF）恢复了这种抑制作用。激活TRPV2的机械力也以强度依赖的方式抑制棕色脂肪细胞的分化，SKF逆转了这种作用。此外，TRPV2配体或机械刺激对脂肪细胞分化的抑制作用在TRPV2KO小鼠细胞中明显较小。此外，钙调磷酸酶抑制剂，环孢素A和FK506，部分逆转TRPV2激活诱导的棕色脂肪细胞分化抑制。因此，我们得出结论，TRPV2可能通过钙调磷酸酶途径部分参与棕色脂肪细胞分化的调节。
Transient receptor potential vanilloid 2 (TRPV2) acts as a Ca2+-permeable non-selective cation channel that has been reported to be sensitive to temperature, mechanical force, and some chemicals. We recently showed that TRPV2 is critical for maintenance of the thermogenic function of brown adipose tissue in mice. However, the involvement of TRPV2 in the differentiation of brown adipocytes remains unexplored. We found that the expression of TRPV2 was dramatically increased during the differentiation of brown adipocytes. Non-selective TRPV2 agonists (2-aminoethoxydiphenyl borate and lysophosphatidylcholine) inhibited the differentiation of brown adipocytes in a dose-dependent manner during the early stage of differentiation of brown adipocytes. The inhibition was rescued by a TRPV2-selective antagonist, SKF96365 (SKF). Mechanical force, which activates TRPV2, also inhibited the differentiation of brown adipocytes in a strength-dependent manner, and the effect was reversed by SKF. In addition, the inhibition of adipocyte differentiation by either TRPV2 ligand or mechanical stimulation was significantly smaller in the cells from TRPV2KO mice. Moreover, calcineurin inhibitors, cyclosporine A and FK506, partially reversed TRPV2 activation-induced inhibition of brown adipocyte differentiation. Thus, we conclude that TRPV2 might be involved in the modulation of brown adipocyte differentiation partially via a calcineurin pathway.