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光动力疗法通过活性氧在成纤维细胞生长因子受体-2b通路中抑制成纤维细胞生长因子-10诱导的角质形成细胞分化和增殖。

Photodynamic therapy inhibit Fibroblast Growth Factor-10 induced keratinocyte differentiation and proliferation through ROS in Fibroblast Growth Factor Receptor-2b pathway.

作者信息

Gozali Maya Valeska, Yi Fei, Zhang Jia-An, Liu Juan, Wu Hong-Jin, Xu Yang, Luo Dan, Zhou Bing-Rong

机构信息

Department of Dermatology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.

出版信息

Sci Rep. 2016 Jun 7;6:27402. doi: 10.1038/srep27402.

Abstract

5-aminolevulinic acid-photodynamic therapy (ALA-PDT) is known to be effective in several skin diseases such as acne, actinic keratoses, condyloma acuminata. However, some detailed mechanisms of ALA-PDT to treat these skin diseases still remain elusive. In this study, we aimed to investigate mechanism of ALA-PDT in in-vitro and in-vivo models. For in vitro, we use human keratinocyte cell line (HaCaT) cells. CCK-8 was used to detect cell proliferation activity, immunofluorescence and western blotting method to detect the content of keratin (K)1, K6, K16, protein kinase C (PKC), fibroblast growth factor receptor-2b (FGFR2b) protein, ELISA and RT-PCR to detect expression of interleukin (IL) 1α in the cell supernatant, and detect reactive oxygen species (ROS). For in vivo, we use 20 rabbits to induce hyperkeratosis acne model in their ear. Dermatoscope was used to see follicle hyperkeratosis and skin biopsy to analyze histology and immunohistochemical of PKC, FGFR2b, K1, K6 and K16. Results from this study suggest that ROS stimulated by ALA-PDT lead to inhibition of FGFR2b pathway in PKC downstream to cause reduction of IL1α expression, and eventually, keratinocytes differentiation and proliferation. Our data thus reveal a treatment mechanism of ALA-PDT underlying hyperkeratosis related dermatoses.

摘要

5-氨基酮戊酸光动力疗法(ALA-PDT)在治疗痤疮、光化性角化病、尖锐湿疣等多种皮肤病方面已被证实有效。然而,ALA-PDT治疗这些皮肤病的一些详细机制仍不清楚。在本研究中,我们旨在研究ALA-PDT在体外和体内模型中的作用机制。体外实验中,我们使用人角质形成细胞系(HaCaT)细胞。采用CCK-8检测细胞增殖活性,免疫荧光和蛋白质印迹法检测角蛋白(K)1、K6、K16、蛋白激酶C(PKC)、成纤维细胞生长因子受体-2b(FGFR2b)蛋白的含量,酶联免疫吸附测定(ELISA)和逆转录-聚合酶链反应(RT-PCR)检测细胞上清液中白细胞介素(IL)1α的表达,并检测活性氧(ROS)。体内实验中,我们使用20只兔子在其耳部诱导角化过度型痤疮模型。使用皮肤镜观察毛囊角化过度情况,并进行皮肤活检以分析PKC、FGFR2b、K1、K6和K16的组织学及免疫组化情况。本研究结果表明,ALA-PDT刺激产生的ROS导致PKC下游的FGFR2b通路受到抑制,从而使IL1α表达减少,并最终导致角质形成细胞的分化和增殖。因此,我们的数据揭示了ALA-PDT治疗角化过度相关皮肤病的作用机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fdd9/4895211/809c7b5ab94d/srep27402-f1.jpg

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