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Abstract Title:

Anti-fibrosis activity of quercetin attenuates rabbit tracheal stenosis via the TGF-β/AKT/mTOR signaling pathway.

Abstract Source:

Life Sci. 2020 Mar 13:117552. Epub 2020 Mar 13. PMID: 32179074

Abstract Author(s):

Yangbao Xiao, Lei Zhou, Tongtong Zhang, Caicheng Qin, Peng Wei, Li Luo, Linzi Luo, Guojun Huang, Anji Chen, Guangnan Liu

Article Affiliation:

Yangbao Xiao

Abstract:

AIMS: This study aimed to explore the possible mechanism of trauma-induced laryngotracheal stenosis and potential protective and therapeutic efficacy of quercetin on trauma-induced laryngotracheal stenosis.

MAIN METHODS: The expression and activity of fibrotic factors [interleukin (IL)-6, IL-8, autophagy related 5 (ATG5), collagen (COL)-1, tumor growth factor (TGF)-β COL-3, microtubule-associated proteins 1A/1B light chain 3A (LC3), and vascular endothelial growth factor (VEGF)] and fibrotic signaling mediators [mammalian target of rapamycin (mTOR) and phosphorylated AKT (pAKT)] were detected by real-time quantitative PCR (qRT-PCR), ELISA, Western blot, and immunohistochemical staining, respectively, in the lipopolysaccharide (LPS)-induced WI-38 (a human embryonic lung fibroblast cell line) cellular fibrotic model and a trauma-induced rabbit tracheal stenosis model, with and without quercetin treatment.

KEY FINDINGS: Pre-treatment with quercetin significantly reversed the LPS-induced upregulation of pro-fibrotic factors (IL-6, IL-8, COL-1, COL-3, LC3) and fibrotic signaling mediators (mTOR and AKT), and it induced the downregulation of ATG5 in the WI-38 cells. Furthermore, the anti-fibrotic activity of quercetin was confirmed in the trauma-induced rabbit tracheal stenosis model. Thus, the nasogastric administration of quercetin attenuated the tracheal stenosis of the rabbit tracheal stenosis model, in addition to effectively reversing an increase in pro-fibrotic factors (VEGF, IL-6, TGF-β, COL-1, and COL-3) and fibrotic signaling mediators (mTOR and AKT), as well as downregulating ATG5 of the rabbit tracheal stenosis model.

SIGNIFICANCE: Quercetin exhibits anti-fibrotic activity by inhibiting pro-fibrotic factors and AKT/mTOR signaling pathway, in addition to activating autophagy activity. This study provided experimental evidence supporting the application of quercetin in tracheal stenosis, clinically.

Study Type : Animal Study
Additional Links
Pharmacological Actions : Anti-Fibrotic : CK(46) : AC(29)

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Sayer Ji
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