瞬时受体电位香草酸 2 介导远红外辐射对扁桃体来源间充质干细胞成脂分化的抑制作用。

Transient receptor potential vanilloid 2 mediates the inhibitory effect of far-infrared irradiation on adipogenic differentiation of tonsil-derived mesenchymal stem cells.

机构信息

Department of Molecular Medicine, College of Medicine, 25 Magokdong-ro-2-gil, Gangseo-gu, Seoul 07804, Republic of Korea; Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Ewha Womans University, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul 07985, Republic of Korea.

Department of Molecular Medicine, College of Medicine, 25 Magokdong-ro-2-gil, Gangseo-gu, Seoul 07804, Republic of Korea; Graduate Program in System Health Science and Engineering, Ewha Womans University, 25 Magokdong-ro-2-gil, Gangseo-gu, Seoul 07804, Republic of Korea.

出版信息

Stem Cell Res. 2021 May;53:102291. doi: 10.1016/j.scr.2021.102291. Epub 2021 Mar 17.

DOI:10.1016/j.scr.2021.102291

PMID:33780730

Abstract

AIMS

Far-infrared (FIR) irradiation inhibits adipogenic differentiation of tonsil-derived mesenchymal stem cells (TMSCs) by activating Ca-dependent protein phosphatase 2B (PP2B), but it stimulates osteogenic differentiation in a PP2B-independent pathway. We investigated the potential involvement of transient receptor potential vanilloid (TRPV) channels, a well-known Ca-permeable channel, in the effects of FIR irradiation on adipogenic or osteogenic differentiation of TMSCs.

METHODS

TMSCs, in the absence or presence of activators or inhibitors, were exposed to FIR irradiation followed by adipogenic or osteogenic differentiation, which was assessed using Oil red O or Alizarin red S staining, respectively. RT-PCR, qRT-PCR, and Western blotting were used to determine gene and protein expression of calcium channels and adipocyte-specific markers.

RESULTS

Treatment with the calcium ionophore ionomycin simulated the inhibitory effect of FIR irradiation on adipogenic differentiation but had no effect on osteogenic differentiation, indicating the involvement of intracellular Ca in adipogenic differentiation. Inhibition of pan-TRP channels using ruthenium red reversed the FIR irradiation-induced inhibition of adipogenic differentiation. Among the TRP channels tested, inhibition of the TRPV2 channel by tranilast or siRNA against TRPV2 attenuated the inhibitory effect of FIR irradiation on adipogenic differentiation, accompanied by a decrease in intracellular Ca levels. By contrast, activation of the TRPV2 channel by probenecid simulated FIR irradiation-induced inhibition of adipogenic differentiation. Expectedly, the stimulatory effect of FIR irradiation on osteogenic differentiation was independent of the TRPV2 channel.

CONCLUSION

Our data demonstrate that the TRPV2 channel is a sensor/receptor for the inhibited adipogenic differentiation of TMSCs associated with FIR irradiation.

摘要

目的

远红外（FIR）辐射通过激活 Ca 依赖性蛋白磷酸酶 2B（PP2B）抑制扁桃体间充质干细胞（TMSCs）的脂肪生成分化，但它通过非依赖于 PP2B 的途径刺激成骨分化。我们研究了瞬时受体电位香草醛（TRPV）通道（一种已知的 Ca 渗透性通道）在 FIR 辐射对 TMSC 脂肪生成或成骨分化的影响中的潜在作用。

方法

在不存在或存在激动剂或抑制剂的情况下，将 TMSCs 暴露于 FIR 辐射下，然后进行脂肪生成或成骨分化，分别用油红 O 或茜素红 S 染色进行评估。使用 RT-PCR、qRT-PCR 和 Western blot 测定钙通道和脂肪细胞特异性标志物的基因和蛋白表达。

结果

使用钙离子载体离子霉素处理模拟了 FIR 辐射对脂肪生成分化的抑制作用，但对成骨分化没有影响，表明细胞内 Ca 参与了脂肪生成分化。用钌红抑制全 TRP 通道逆转了 FIR 辐射诱导的脂肪生成分化抑制。在所测试的 TRP 通道中，用曲尼司特或针对 TRPV2 的 siRNA 抑制 TRPV2 通道减弱了 FIR 辐射对脂肪生成分化的抑制作用，同时细胞内 Ca 水平降低。相比之下，用丙磺舒激活 TRPV2 通道模拟了 FIR 辐射诱导的脂肪生成分化抑制。预期 FIR 辐射对成骨分化的刺激作用与 TRPV2 通道无关。