褪黑素
自噬
PI3K/AKT/mTOR通路
蛋白激酶B
氯吲哚
成纤维细胞
细胞生物学
内分泌学
褪黑激素受体
内科学
生物
化学
癌症研究
信号转导
细胞凋亡
医学
细胞培养
生物化学
遗传学
作者
Yunxian Dong,Xiaoling Cao,Jinsheng Huang,Zhicheng Hu,Chufen Chen,Miao Chen,Long Qian,Zhongye Xu,Dongming Lv,Yanchao Rong,Sheng-Kang Luo,Haibin Wang,Wuguo Deng,Bing Tang
标识
DOI:10.1016/j.bbadis.2023.166887
摘要
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.
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