Department of Anatomy & Cell Biology, Gachon University College of Medicine, Incheon 21936, Korea.
Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine, Incheon 21999, Korea.
Int J Mol Sci. 2021 Oct 3;22(19):10724. doi: 10.3390/ijms221910724.
Autophagy is involved in the degradation of melanosomes and the determination of skin color. TLR4 and tumor necrosis factor (TNF) signaling upregulates NF-kB expression, which is involved in the upregulation of mTOR. The activation of mTOR by UV-B exposure results in decreased autophagy, whereas radiofrequency (RF) irradiation decreases TLR4 and TNF receptor (TNFR) expression. We evaluated whether RF decreased skin pigmentation by restoring autophagy by decreasing the expression of TLR4 or TNFR/NF-κB/mTOR in the UV-B-irradiated animal model. UV-B radiation induced the expressions of TNFR, TLR, and NF-κB in the skin, which were all decreased by RF irradiation. RF irradiation also decreased phosphorylated mTOR expression and upregulated autophagy initiation factors such as FIP200, ULK1, ULK2, ATG13, and ATG101 in the UV-B-irradiated skin. Beclin 1 expression and the expression ratio of LC3-I to LC3-II were increased by UV-B/RF irradiation. Furthermore, melanin-containing autophagosomes increased with RF irradiation. Fontana-Masson staining showed that the amount of melanin deposition in the skin was decreased by RF irradiation. This study showed that RF irradiation decreased skin pigmentation by restoring melanosomal autophagy, and that the possible signal pathways which modulate autophagy could be TLR4, TNFR, NF-κB, and mTOR.
自噬参与黑色素体的降解和肤色的决定。TLR4 和肿瘤坏死因子 (TNF) 信号通路上调 NF-κB 的表达,从而参与 mTOR 的上调。UV-B 暴露激活 mTOR 会导致自噬减少,而射频 (RF) 辐射会降低 TLR4 和 TNF 受体 (TNFR) 的表达。我们评估了 RF 是否通过降低 TLR4 或 TNFR/NF-κB/mTOR 的表达来恢复自噬,从而减少皮肤色素沉着,在 UV-B 照射的动物模型中。UV-B 辐射诱导皮肤中 TNFR、TLR 和 NF-κB 的表达,RF 辐射均可降低其表达。RF 辐射还降低了磷酸化 mTOR 的表达,并上调了 UV-B 照射皮肤中自噬起始因子,如 FIP200、ULK1、ULK2、ATG13 和 ATG101。Beclin 1 表达和 LC3-I 到 LC3-II 的表达比值增加了 UV-B/RF 辐射。此外,含有黑色素的自噬体随着 RF 辐射而增加。Fontana-Masson 染色显示 RF 辐射减少了皮肤中黑色素的沉积量。这项研究表明,RF 辐射通过恢复黑色素体自噬来减少皮肤色素沉着,调节自噬的可能信号通路可能是 TLR4、TNFR、NF-κB 和 mTOR。