NDLI: Deglycosylated Azithromycin Attenuates Bleomycin-Induced Pulmonary Fibrosis via the TGF-β1 Signaling Pathway

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Deglycosylated Azithromycin Attenuates Bleomycin-Induced Pulmonary Fibrosis via the TGF-β1 Signaling Pathway

Content Provider	MDPI
Author	Ruan, Hao Gao, Shaoyan Li, Shuangling Luan, Jiaoyan Jiang, Qiuyan Li, Xiaohe Yin, Huijun Zhou, Honggang Yang, Cheng
Copyright Year	2021
Description	Idiopathic pulmonary fibrosis (IPF) is a progressive, life-threatening lung disease characterized by the proliferation of myofibroblasts and deposition of extracellular matrix that results in irreversible distortion of the lung structure and the formation of focal fibrosis. The molecular mechanism of IPF is not fully understood, and there is no satisfactory treatment. However, most studies suggest that abnormal activation of transforming growth factor-β1 (TGF-β1) can promote fibroblast activation and epithelial to mesenchymal transition (EMT) to induce pulmonary fibrosis. Deglycosylated azithromycin (Deg-AZM) is a compound we previously obtained by removing glycosyls from azithromycin; it was demonstrated to exert little or no antibacterial effects. Here, we discovered a new function of Deg-AZM in pulmonary fibrosis. In vivo experiments showed that Deg-AZM could significantly reduce bleomycin-induced pulmonary fibrosis and restore respiratory function. Further study revealed the anti-inflammatory and antioxidant effects of Deg-AZM in vivo. In vitro experiments showed that Deg-AZM inhibited TGF-β1 signaling, weakened the activation and differentiation of lung fibroblasts, and inhibited TGF-β1-induced EMT in alveolar epithelial cells. In conclusion, our findings show that Deg-AZM exerts antifibrotic effects by inhibiting TGF-β1-induced myofibroblast activation and EMT.
Starting Page	2820
e-ISSN	14203049
DOI	10.3390/molecules26092820
Journal	Molecules
Issue Number	9
Volume Number	26
Language	English
Publisher	MDPI
Publisher Date	2021-05-10
Access Restriction	Open
Subject Keyword	Molecules Respiratory System Deglycosylated Azithromycin Pulmonary Fibrosis Transforming Growth Factor-β1 Epithelial To Mesenchymal Transition Inflammation
Content Type	Text
Resource Type	Article

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