Department of Dermatology and Venereology and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, P.R. China.
School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, P.R. China.
Cell Death Dis. 2019 Jan 8;10(1):19. doi: 10.1038/s41419-018-1261-y.
Ultraviolet radiation is markedly increased because of pollution and the depletion of the stratospheric ozone layer. Excessive exposure to sunlight can negatively affect the skin, resulting in sunburn, photo-aging, or skin cancer. In this study, we first determined the photoprotective effect of sanshool, a major component in Zanthoxylum bungeanum, on UVB-irradiated responses in human dermal fibroblasts (HDFs) and nude mouse. We found that sanshool treatment can protect cells against the effects of UVB irradiation by (i) increasing cell viability, (ii) inhibiting MMP expression, and (iii) inducing autophagy. We also used the recombinant CSF2 or anti-CSF2 antibody co-cultured with human dermal fibroblasts (HDFs) and found that CSF2 contributes to sanshool-induced autophagy. Sanshool hindered the UVB-induced activation of JAK2-STAT3 signaling in HDFs, thereby inhibiting the expression of MMPs and activation of autophagic flux. Exposure of the dorsal skin of hairless mice to UVB radiation and subsequent topical application of sanshool delayed the progression of skin inflammation, leading to autophagy and inhibiting the activation of JAK2-STAT3 signaling. These results provide a basis for the study of the photoprotective effect of sanshool and suggest that it can be potentially used as an agent against UVB-induced skin damage in humans.
由于污染和平流层臭氧消耗，紫外线辐射明显增加。过度暴露在阳光下会对皮肤产生负面影响，导致晒伤、光老化或皮肤癌。在这项研究中，我们首先确定了花椒中的主要成分花椒素对 UVB 照射人真皮成纤维细胞（HDF）和裸鼠的保护作用。我们发现花椒素处理可以通过以下方式保护细胞免受 UVB 照射的影响：（i）增加细胞活力，（ii）抑制 MMP 表达，（iii）诱导自噬。我们还使用重组 CSF2 或抗 CSF2 抗体与人类真皮成纤维细胞（HDF）共培养，发现 CSF2 有助于花椒素诱导的自噬。花椒素抑制了 HDF 中 UVB 诱导的 JAK2-STAT3 信号的激活，从而抑制了 MMP 的表达和自噬流的激活。将无毛小鼠背部皮肤暴露于 UVB 辐射下，随后局部应用花椒素，可延缓皮肤炎症的进展，诱导自噬并抑制 JAK2-STAT3 信号的激活。这些结果为花椒素的光保护作用研究提供了依据，并表明其可能被用作人类对抗 UVB 诱导皮肤损伤的药物。
