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一种新型二氢卟吩e6衍生物介导的光动力疗法STBF-PDT通过TGF-β途径逆转光老化。

A novel chlorin e6 derivative-mediated photodynamic therapy STBF-PDT reverses photoaging via the TGF-β pathway.

作者信息

Shi Jingjuan, Zeng Qingyu, Wang Peiru, Chang Qihang, Huang Jianhua, Wu Minfeng, Wang Xiuli, Wang Hongwei

机构信息

Department of Dermatology, Huadong Hospital, Fudan University, Shanghai 200040, China.

Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai 200050, China.

出版信息

Photodiagnosis Photodyn Ther. 2023 Mar;41:103321. doi: 10.1016/j.pdpdt.2023.103321. Epub 2023 Feb 3.

DOI:10.1016/j.pdpdt.2023.103321
PMID:36738905
Abstract

OBJECTIVE

Photoaging is characterized by wrinkles in the skin and the deterioration of the skin barrier function, mainly caused by long-term exposure to ultraviolet (UV) radiation. Photodynamic therapy (PDT) has been shown to treat photoaging. The novel photosensitizer ShengTaiBuFen(STBF) is a derived substance of Chlorin e6(Ce6) that can exert photodynamic effects directly. In this study, we investigated the availability and the mechanism of STBF-PDT in the treatment of photoaging.

METHODS

Fluorophotometer was used to determine therapeutic parameters for in vivo experiments. Camera photographs, dermoscopy, HE and Masson staining, skin pH, trans epidermal water loss (TEWL), epidermal water content, and sebum testing were used together to evaluate the results of the treatment. Dark toxicity and therapeutic parameters for in vitro experiments were determined by CCK8 analysis. Scratch assay was used to identify the cell migration of STBF-PDT on HaCaT cells. qPCR and Western blot were used to evaluate the TGF-β/Smad signaling pathway in human dermal fibroblast (HDF) cells.

RESULTS

We investigated the optimal STBF concentration and time of incubation in vivo and in vitro experiments. STBF-PDT improved the skin phenotype of photoaged mice. The skin of photoaged mice treated with 80 J/cm STBF-PDT became smooth, while skin flakes were reduced. The epidermis of STBF-PDT-treated mice was thinner, and the cells were neatly arranged, with increased dermal collagen. In vitro, STBF-PDT promoted the migration of HaCaT cells below a light dose of 0.1 J/cm. HDF cells co-cultured with HaCaT cells treated with low-dose STBF-PDT showed activation of the TGF-β pathway.

CONCLUSION

As a novel photosensitizer, STBF-mediated low-dose PDT could reverse photoaging via the TGF-β pathway.

摘要

目的

光老化的特征是皮肤出现皱纹以及皮肤屏障功能受损,主要由长期暴露于紫外线(UV)辐射引起。光动力疗法(PDT)已被证明可用于治疗光老化。新型光敏剂盛泰部分(STBF)是二氢卟吩e6(Ce6)的衍生物,可直接发挥光动力效应。在本研究中,我们探讨了STBF-PDT治疗光老化的有效性及作用机制。

方法

使用荧光光度计确定体内实验的治疗参数。综合运用相机拍照、皮肤镜检查、苏木精-伊红(HE)和马松染色、皮肤pH值、经表皮水分流失(TEWL)、表皮水分含量及皮脂检测来评估治疗效果。通过CCK8分析确定体外实验的暗毒性和治疗参数。划痕试验用于鉴定STBF-PDT对HaCaT细胞的细胞迁移作用。采用qPCR和蛋白质印迹法评估人皮肤成纤维细胞(HDF)中的转化生长因子-β(TGF-β)/Smad信号通路。

结果

我们在体内和体外实验中研究了STBF的最佳浓度和孵育时间。STBF-PDT改善了光老化小鼠的皮肤表型。用80 J/cm的STBF-PDT治疗的光老化小鼠皮肤变得光滑,皮屑减少。经STBF-PDT治疗的小鼠表皮变薄,细胞排列整齐,真皮胶原蛋白增加。在体外,在光剂量低于0.1 J/cm时,STBF-PDT促进了HaCaT细胞的迁移。与用低剂量STBF-PDT处理的HaCaT细胞共培养的HDF细胞显示TGF-β通路激活。

结论

作为一种新型光敏剂,STBF介导的低剂量PDT可通过TGF-β通路逆转光老化。

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