Tuo Jiang, Wang Qianqian, Zouboulis Christos C, Liu Ye, Ma Ying, Ma Li, Ying Jiayi, Zhang Chengfeng, Xiang Leihong
Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, 200040, PR China.
Departments of Dermatology, Venereology, Allergology and Immunology Dessau Medical Center Auenweg 38, 06847 Dessau, Germany.
Photodiagnosis Photodyn Ther. 2017 Jun;18:295-301. doi: 10.1016/j.pdpdt.2017.03.006. Epub 2017 Mar 19.
5-Aminolevulinic acid mediated -photodynamic therapy (ALA-PDT) is known to be effective in treating acne vulgaris and other sebaceous gland-related diseases. However, the therapeutic mechanisms of ALA-PDT still remain undetermined. In this study, we aimed to investigate the effects and mechanisms of ALA-PDT on the cell growth and lipogenesis of human SZ95 sebocytes.
Human SZ95 sebocytes were treated with different concentration of ALA-PDT.CCK-8 assay was used to detect cell proliferation activity. Fluorescence microscope and flow cytometry were used to observe the secretion of lipids in SZ95 cells after Nile red staining. Western blotting was used to detect and analyze the protein expression level of P-p70 S6K/p70 S6K, P-4E-BP1/4E-BP1, SREBP-1, PPARγ, P-mTOR/mTOR, and P-Raptor/Raptor. Mean while, mTOR pathway activator IGF-1 and mTORC1 inhibitor rapamycin were added to observe the interferences on the ALA-PDT treatment of SZ95 cells.
ALA-PDT suppressed the cell growth and reduced the secretion of lipids in a dose-dependent manner in SZ95 cells. ALA-PDT reduced the protein levels of P-p70 S6K (T389), SREBP-1, PPARγ, P-mTOR and P-Raptor. IGF-1 had counter effects on ALA-PDT, and rapamycin enhanced the effects of ALA-PDT in SZ95 cells in suppressing the cell growth and reducing the secretion of lipids.
ALA-PDT suppressed the cell growth in SZ95 cells by mTOR-p70 S6K(T389) signaling and reduced the lipogenesis in SZ95 cells by mTOR-SREBP-1/PPARγ signaling. Sebaceous glands atrophy and reduction of sebum secretion after ALA-PDT may be caused by the suppression of lipogenesis and cell growth in sebocytes.
5-氨基酮戊酸介导的光动力疗法（ALA-PDT）已知对寻常痤疮及其他皮脂腺相关疾病有效。然而，ALA-PDT的治疗机制仍未明确。在本研究中，我们旨在探究ALA-PDT对人SZ95皮脂腺细胞生长及脂质生成的影响和机制。
用不同浓度的ALA-PDT处理人SZ95皮脂腺细胞。采用CCK-8法检测细胞增殖活性。用荧光显微镜和流式细胞术观察尼罗红染色后SZ95细胞中脂质的分泌情况。用蛋白质免疫印迹法检测并分析P-p70 S6K/p70 S6K、P-4E-BP1/4E-BP1、SREBP-1、PPARγ、P-mTOR/mTOR和P-Raptor/Raptor的蛋白表达水平。同时，添加mTOR通路激活剂IGF-1和mTORC1抑制剂雷帕霉素，观察其对ALA-PDT处理SZ95细胞的干扰作用。
ALA-PDT以剂量依赖性方式抑制SZ95细胞的生长并减少脂质分泌。ALA-PDT降低了P-p70 S6K（T389）、SREBP-1、PPARγ、P-mTOR和P-Raptor的蛋白水平。IGF-1对ALA-PDT有拮抗作用，雷帕霉素增强了ALA-PDT对SZ95细胞生长的抑制作用及脂质分泌的减少作用。
ALA-PDT通过mTOR-p70 S6K（T389）信号通路抑制SZ95细胞的生长，并通过mTOR-SREBP-1/PPARγ信号通路减少SZ95细胞的脂质生成。ALA-PDT后皮脂腺萎缩及皮脂分泌减少可能是由于皮脂腺细胞脂质生成和细胞生长受到抑制所致。
