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melatonin influences the biological characteristics of keloid fibroblasts through the erk and smad signalling pathways

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Burns & Trauma 2023年第1期11卷 258-272页

作者： Shaobin Huang Wuguo Deng Yunxian Dong Zhicheng Hu Yi Zhang Peng Wang Xiaoling Cao Miao Chen Pu Cheng Hailin Xu Wenkai Zhu Bing Tang Jiayuan Zhu Department of Burn First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080China Department of Cosmetic and Plastic Surgery The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510655China Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhou 510060China Department of Burn and Plastic Surgery Affiliated Hospital of Nantong UniversityNantong 226001China Department of Obstetrics and Gynecology School of MedicineStanford UniversityStanfordCA 94305United States

Background:Keloids are abnormal fibrous hyperplasias that are difficult to *** can be used to inhibit the development of certain fibrotic diseases but has never been used to treat *** aimed to discover the effects and mechanisms of melatonin in keloid fibroblasts(KFs).Methods:Flow cytometry,CCK-8 assays,western blotting,wound-healing assays,transwell assays,collagen gel contraction assays and immunofluorescence assays were applied to demonstrate the effects and mechanisms of melatonin in fibroblasts derived from normal skin,hypertrophic scars and *** therapeutic potential of the combination of melatonin and 5-fluorouracil(5-FU)was investigated in ***:melatonin significantly promoted cell apoptosis and inhibited cell proliferation,migration and invasion,contractile capability and collagen production in *** mechanistic studies demonstrated that melatonin could inhibit the cAMP/PKA/erk and smad pathways through the membrane receptor MT2 to alter the biological characteristics of ***,the combination of melatonin and 5-FU remarkably promoted cell apoptosis and inhibited cell migration and invasion,contractile capability and collagen production in ***,5-FU suppressed the phosphorylation of Akt,mTOR,smad3 and erk,and melatonin in combination with 5-FU markedly suppressed the activation of the Akt,erk and smad ***:Collectively,melatonin may inhibit the erk and smad pathways through the mem-brane receptor MT2 to alter the cell functions of KFs,while combination with 5-FU could exert even more inhibitory effects in KFs through simultaneous suppression of multiple signalling pathways.

关键词： Keloid fibroblast,melatonin,5-fluorouracil,erk,smad Signalling pathways Hyperplasias Phosphorylation

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