Melatonin influences the biological characteristics of keloid fibroblasts through the Erk and Smad signalling pathways

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

doi:10.1093/burnst/tkad005

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Melatonin influences the biological characteristics of keloid fibroblasts through the Erk and Smad signalling pathways

更新时间：2023-05-16

- Melatonin influences the biological characteristics of keloid fibroblasts through the Erk and Smad signalling pathways
- Burns & Trauma Vol. 11, Issue 1, (2023)
- 作者机构：
  
  1. Department of Burn, First Affiliated Hospital of Sun Yat-sen University
  2. Department of Cosmetic and Plastic Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University
  3. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China
  4. Collaborative Innovation Center for Cancer Medicine
  5. Department of Burn and Plastic Surgery, Affiliated Hospital of Nantong University
  6. Department of Obstetrics and Gynecology, School of Medicine, Stanford University
- 作者简介：
- 基金信息：
- DOI：10.1093/burnst/tkad005
  CLC：
- Published：2023，
  
  Published Online：1 March 2023，
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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, Melatonin influences the biological characteristics of keloid fibroblasts through the Erk and Smad signalling pathways, Burns & Trauma, Volume 11, 2023, tkad005, https://doi.org/10.1093/burnst/tkad005
DOI：

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, Melatonin influences the biological characteristics of keloid fibroblasts through the Erk and Smad signalling pathways, Burns & Trauma, Volume 11, 2023, tkad005, https://doi.org/10.1093/burnst/tkad005 DOI：

摘要

Abstract

BackgroundKeloids are abnormal fibrous hyperplasias that are difficult to treat. Melatonin can be used to inhibit the development of certain fibrotic diseases but has never been used to treat keloids. We aimed to discover the effects and mechanisms of melatonin in keloid fibroblasts (KFs).MethodsFlow 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 keloids. The therapeutic potential of the combination of melatonin and 5-fluorouracil (5-FU) was investigated in KFs.ResultsMelatonin significantly promoted cell apoptosis and inhibited cell proliferation

migration and invasion

contractile capability and collagen production in KFs. Further 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 KFs. Moreover

the combination of melatonin and 5-FU remarkably promoted cell apoptosis and inhibited cell migration and invasion

contractile capability and collagen production in KFs. Furthermore

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 pathways.ConclusionsCollectively

melatonin may inhibit the Erk and Smad pathways through the membrane 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

Keywords

KeloidFibroblastMelatonin5-fluorouracilERKSmadSignalling pathwaysHyperplasiasPhosphorylation

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