2. Academic Validation
  3. Melatonin inhibits fibroblast cell functions and hypertrophic scar formation by enhancing autophagy through the MT2 receptor-inhibited PI3K/Akt /mTOR signaling

Melatonin inhibits fibroblast cell functions and hypertrophic scar formation by enhancing autophagy through the MT2 receptor-inhibited PI3K/Akt /mTOR signaling

  • Biochim Biophys Acta Mol Basis Dis. 2023 Sep 21;1870(1):166887. doi: 10.1016/j.bbadis.2023.166887.
Yunxian Dong 1,  Xiaoling Cao 2,  Jinsheng Huang 3,  Zhicheng Hu 2,  Chufen Chen 2,  Miao Chen 3,  Qian Long 3,  Zhongye Xu 2,  Dongming Lv 2,  Yanchao Rong 2,  Shengkang Luo 4,  Haibin Wang 4,  Wuguo Deng 5,  Bing Tang 6
Affiliations

Affiliations

  • 1 Department of Burns, Wound Repair and Reconstruction, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Department of Plastic and Reconstructive Surgery, Guangdong Second Provincial General Hospital, Guangzhou, China.
  • 2 Department of Burns, Wound Repair and Reconstruction, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
  • 3 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Canter of Cancer Medicine, Guangzhou, China.
  • 4 Department of Plastic and Reconstructive Surgery, Guangdong Second Provincial General Hospital, Guangzhou, China.
  • 5 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Canter of Cancer Medicine, Guangzhou, China. Electronic address: dengwg@sysucc.org.cn.
  • 6 Department of Burns, Wound Repair and Reconstruction, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. Electronic address: tangbing@mail.sysu.edu.cn.
PMID: 37739092 DOI: 10.1016/j.bbadis.2023.166887
Abstract

Hypertrophic scar (HS) is a fibrotic skin condition and characterized by abnormal proliferation of myofibroblasts and accumulation of extracellular matrix. Melatonin, an endogenous hormone, can alleviate fibrosis in multiple models of diseases. This study examined the effect of melatonin on fibrosis in primary fibroblasts from human HS (HSFs) and a rabbit ear model and potential mechanisms. Melatonin treatment significantly decreased the migration and contraction capacity, collagen and α-smooth muscle actin (α-SMA) production in HSFs. RNA-sequencing and bioinformatic analyses indicated that melatonin modulated the expression of genes involved in Autophagy and oxidative stress. Mechanistically, melatonin treatment attenuated the Akt/mTOR activation through affecting the binding of MT2 receptor with PI3K to enhance Autophagy, decreasing fibrogenic factor production in HSFs. Moreover, melatonin treatment inhibited HS formation in rabbit ears by enhancing Autophagy. The anti-fibrotic effects of melatonin were abrogated by treatment with an Autophagy Inhibitor (3-methyladenine, 3-MA), an Akt Activator (SC79), or an MT2 selective antagonist (4-phenyl-2propionamidotetralin, 4-P-PDOT). Therefore, melatonin may be a potential drug for prevention and treatment of HS.

Keywords

Autophagy; Fibroblast; Fibrosis; Hypertrophic scar; Melatonin; PI3K/Akt/mTOR signaling.

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