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Melatonin attenuates epidermal growth factor-induced cathepsin S expression in ARPE-19 cells: Implications for proliferative vitreoretinopathy.
Journal of Pineal Research ( IF 10.3 ) Pub Date : 2019-11-10 , DOI: 10.1111/jpi.12615
Shun-Fa Yang,Yong-Syuan Chen,Hsiang-Wen Chien,Kai Wang,Chia-Liang Lin,Hui-Ling Chiou,Chia-Yi Lee,Pei-Ni Chen,Yi-Hsien Hsieh

Abnormal proliferation and motility of retinal pigment epithelial cells leads to proliferative vitreoretinopathy (PVR). Melatonin is a known effective antitumour and anti-invasive agent, but whether it affects the formation and underlying mechanisms of PVR remains unclear. In this study, the results of the MTT assay, colony formation and propidium iodide (PI) staining with flow cytometry revealed that melatonin dose dependently inhibited epidermal growth factor (EGF)-induced proliferation of human ARPE-19 cells. Furthermore, melatonin reduced EGF-induced motility by suppressing cathepsin S (CTSS) expression. Pretreatment with ZFL (a CTSS inhibitor) or overexpression of CTSS (pCMV-CTSS) significantly inhibited EGF-induced cell motility when combined with melatonin. Epidermal growth factor induced the phosphorylation of AKT(S473)/mTOR (S2448) and transcription factor (c-Jun/Sp1) signaling pathways. Pretreatment of LY294002 (a PI3K inhibitor) or rapamycin (an mTOR inhibitor) markedly reduced EGF-induced motility and p-AKT/p-mTOR/c-Jun/Sp1 expression when combined with melatonin. Taken together, these data indicate that melatonin inhibited EGF-induced proliferation and motility of human ARPE-19 cells by activating the AKT/mTOR pathway, which is dependent on CTSS modulation of c-Jun/Sp1 signalling. Melatonin may be a promising therapeutic drug against PVR.

中文翻译:

褪黑素减弱ARPE-19细胞中表皮生长因子诱导的组织蛋白酶S的表达:对增殖性玻璃体视网膜病变的影响。

视网膜色素上皮细胞的异常增殖和运动导致增殖性玻璃体视网膜病变(PVR)。褪黑激素是已知的有效抗肿瘤和抗侵袭剂,但是尚不清楚它是否影响PVR的形成和潜在机制。在这项研究中,MTT分析,集落形成和碘化丙啶(PI)染色与流式细胞术的结果表明,褪黑激素剂量依赖性地抑制了表皮生长因子(EGF)诱导的人ARPE-19细胞的增殖。此外,褪黑素通过抑制组织蛋白酶S(CTSS)的表达降低了EGF诱导的运动。与褪黑素联合使用ZFL(CTSS抑制剂)预处理或CTSS过表达(pCMV-CTSS)可以显着抑制EGF诱导的细胞运动。表皮生长因子诱导AKT(S473)/ mTOR(S2448)和转录因子(c-Jun / Sp1)信号通路的磷酸化。与褪黑素联合使用时,LY294002(PI3K抑制剂)或雷帕霉素(mTOR抑制剂)的预处理可显着降低EGF诱导的运动性和p-AKT / p-mTOR / c-Jun / Sp1表达。综上所述,这些数据表明褪黑激素通过激活AKT / mTOR途径来抑制EGF诱导的人ARPE-19细胞的增殖和运动,这取决于c-Jun / Sp1信号的CTSS调节。褪黑激素可能是针对PVR的有前途的治疗药物。这些数据表明,褪黑素通过激活AKT / mTOR途径来抑制EGF诱导的人ARPE-19细胞的增殖和运动,这取决于c-Jun / Sp1信号的CTSS调节。褪黑激素可能是针对PVR的有前途的治疗药物。这些数据表明,褪黑素通过激活AKT / mTOR途径来抑制EGF诱导的人ARPE-19细胞的增殖和运动,这取决于c-Jun / Sp1信号的CTSS调节。褪黑激素可能是针对PVR的有前途的治疗药物。
更新日期:2019-11-10
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