ReferenceID 6336
Tetrandrine Modulates Rheb-mTOR Signaling-Mediated Selective Autophagy and Protects Pulmonary Fibrosis
Front Pharmacol
Idiopathic pulmonary fibrosis is a progressive fatal disease characterized by interstitial remodeling, with high lethality and a lack of effective medical therapies. Tetrandrine has been proposed to present anti-fibrotic
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Record Fields
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- Reference Id
- 6336
- Evidence Id
- 22926
- Core Evidence Id
- 22926
- Source Reference Id
- 5946
- Herb2 Reference Id
- HBREF006743
- Subject Paper Key
- HBIN046110_34880752
- Pubmed Id
- 34880752
- Doi
- 10.3389/fphar.2021.739220
- Paper Title
- Tetrandrine Modulates Rheb-mTOR Signaling-Mediated Selective Autophagy and Protects Pulmonary Fibrosis
- Paper Abstract
- Idiopathic pulmonary fibrosis is a progressive fatal disease characterized by interstitial remodeling, with high lethality and a lack of effective medical therapies. Tetrandrine has been proposed to present anti-fibrotic effects, but the efficacy and mechanisms have not been systematically evaluated. We sought to study the potential therapeutic effects and mechanisms of tetrandrine against lung fibrosis. The anti-fibrotic effects of tetrandrine were evaluated in bleomycin-induced mouse models and TGF-beta1-stimulated murine lung fibroblasts. We performed Chromatin Immunoprecipitation (ChIP), Immunoprecipitation (IP), and mRFP-GFP-MAP1LC3B adenovirus construct to investigate the novel mechanisms of tetrandrine-induced autophagy. Tetrandrine decreased TGF-beta1-induced expression of alpha-smooth muscle actin, fibronectin, vimentin, and type 1 collagen and proliferation in fibroblasts. Tetrandrine restored TGF-beta1-induced impaired autophagy flux, accompanied by enhanced interaction of SQSTM1 and MAP1LC3-II. ChIP studies revealed that tetrandrine induced autophagy via increasing binding of NRF2 and SQSTM1 promoter. Furthermore, tetrandrine inhibited TGF-beta1-induced phosphorylation of mTOR by reducing activation of Rheb. In vivo tetrandrine suppressed the bleomycin-induced expression of fibrotic markers and improved pulmonary function. Our data suggest that protective effect of tetrandrine against lung fibrosis might be through promoting Rheb-mTOR and NRF2-SQSTM1 mediated autophagy. Tetrandrine may thus be potentially employed as a novel therapeutic medicine against IPF.
- Journal
- Front Pharmacol
- Publish Year
- 2021
- Experiment Subject
- mouse; tgf-beta1-stimulated murine lung fibroblasts
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Idiopathic Pulmonary Fibrosis; Lung Fibrosis
- Paper Title Cn
- Paper Title En
- Tetrandrine Modulates Rheb-mTOR Signaling-Mediated Selective Autophagy and Protects Pulmonary Fibrosis
- Bilingual Status
- semi_complete