Astragalin inhibits autophagy-associated airway epithelial fibrosis

Cho, In-Hee; Choi, Yong‐Kook; Gong, Ju‐Hyun; Shin, Dong‐Bin; Kang, Min‐Kyung; Kang, Young‐Hee

doi:10.1186/s12931-015-0211-9

Cited by 62 publications

(52 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ovalbumin (OVA) is widely used as an animal experimental model of asthma. Inhalation of OVA in mice increases levels of autophagic markers , including beclin‐1 in mouse airway tissues, which has been confirmed by Cy3‐red staining . In OVA‐challenged animals, both α‐actin smooth muscle (α‐SMA) and LC3A/B increased in the airway subepithelial space which highlights the role of autophagy, and possibly epithelial–mesenchymal transition (EMT) induction .…”

Section: Autophagy and Animal Models Of Asthmamentioning

confidence: 74%

Autophagy in airway diseases: a new frontier in human asthma?

Zeki¹,

Yeganeh

Kenyon³

et al. 2015

Allergy

View full text Add to dashboard Cite

The study of autophagy (‘self-eating’), a fundamental cell fate pathway involved in physiological and pathological subcellular processes, opens a new frontier in the continuous search for novel therapies for human asthma. Asthma is a complex syndrome with different disease phenotypes. Autophagy plays a central role in cell physiology, energy and metabolism, and cell survival. Autophagy’s hallmark is the formation of double-membrane autophagic autophagosomes, and this process is operational in airway epithelial and mesenchymal cells in asthma. Genetic associations between autophagy genes and asthma have been observed including single nucleotide polymorphisms in Atg5 which correlate with reduced lung function. Immune mechanisms important in asthma such as Th2 cells and eosinophils also manifest autophagy. Lastly, we address the role of autophagy in extracellular matrix deposition and fibrosis in asthmatic airways remodeling, a pathologic process still without effective therapy, and discuss potential pharmacologic inhibitors. We end by offering two opposing but plausible hypotheses as to how autophagy may be directly involved in airway fibrosis.

show abstract

Section: Autophagy and Animal Models Of Asthmamentioning

confidence: 74%

Autophagy in airway diseases: a new frontier in human asthma?

Zeki¹,

Yeganeh

Kenyon³

et al. 2015

Allergy

View full text Add to dashboard Cite

show abstract

“…16 In addition, the induction of autophagy directly impairs the expression of antiviral type III IFNL1/IFNλ1 (interferon, lambda 1) and enhances rhinovirus infection in airway epithelial cells, thus functioning as a novel mechanism to hinder the host antiviral defense against respiratory viral infection in the lung. 17 Furthermore, autophagy is believed to serve as a cellular signaling event to promote the transforming growth factor b 1-mediated airway remodeling and loss of lung function in asthma.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, manipulating autophagic pathways and their regulatory components might lead to the development of therapeutics for lung diseases. 16,17 However, the function of autophagy in the context of PM2.5-induced airway responses, especially the production of proinflammatory factors, has not been explored.…”

Section: Introductionmentioning

confidence: 99%

TP53-dependent autophagy links the ATR-CHEK1 axis activation to proinflammatory VEGFA production in human bronchial epithelial cells exposed to fine particulate matter (PM2.5)

Wang

et al. 2016

Autophagy

View full text Add to dashboard Cite

Epidemiological and clinical studies have increasingly shown that fine particulate matter (PM2.5) is associated with a number of pathological respiratory diseases, such as bronchitis, asthma, and chronic obstructive pulmonary disease, which share the common feature of airway inflammation induced by particle exposure. Thus, understanding how PM2.5 triggers inflammatory responses in the respiratory system is crucial for the study of PM2.5 toxicity. In the current study, we found that exposing human bronchial epithelial cells (immortalized Beas-2B cells and primary cells) to PM2.5 collected in the winter in Wuhan, a city in southern China, induced a significant upregulation of VEGFA (vascular endothelial growth factor A) production, a signaling event that typically functions to control chronic airway inflammation and vascular remodeling. Further investigations showed that macroautophagy/autophagy was induced upon PM2.5 exposure and then mediated VEGFA upregulation by activating the SRC (SRC proto-oncogene, non-receptor tyrosine kinase)-STAT3 (signal transducer and activator of transcription 3) pathway in bronchial epithelial cells. By exploring the upstream signaling events responsible for autophagy induction, we revealed a requirement for TP53 (tumor protein p53) activation and the expression of its downstream target DRAM1 (DNA damage regulated autophagy modulator 1) for the induction of autophagy. These results thus extend the role of TP53-DRAM1-dependent autophagy beyond cell fate determination under genotoxic stress and to the control of proinflammatory cytokine production. Moreover, PM2.5 exposure strongly induced the activation of the ATR (ATR serine/threonine kinase)-CHEK1/CHK1 (checkpoint kinase 1) axis, which subsequently triggered TP53-dependent autophagy and VEGFA production in Beas-2B cells. Therefore, these findings suggest a novel link between processes regulating genomic integrity and airway inflammation via autophagy induction in bronchial epithelial cells under PM2.5 exposure.

show abstract

“…Quercetin is a compound that plays an important role in inflammation, cancer, aging, cell signaling, proapoptotic effects, antiproliferative effects, antioxidant effects, and growth suppression [35,36]. Astragalin (MW � 448.41, OB (%) � 14.03, Caco-2 � -1.34, DL � 0.74, and HL � N/A) has been reported to inhibit autophagosome formation in airways [37]. Honokiol (MW � 266.36, OB (%) � 60.67, Caco-2 � 1.43, DL � 0.15, and HL � 2.88) has been shown to have antitumorigenic, anti-inflammatory, and antioxidant effects [38][39][40].…”

Section: Collecting 10 Cml-related Active Compounds and Systemic Pharmentioning

confidence: 99%

Systemic Pharmacological Approach to Identification and Experimental Verification of the Effect of Anisi Stellati Fructus Extract on Chronic Myeloid Leukemia Cells

Kim

Suh

Ahn

et al. 2019

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Anisi stellati fructus (ASF) is the dried fruit of the Illicium verum Hook.f. tree. e aim of this research was to evaluate the antileukemic effect of ASF on chronic myeloid leukemia (CML) cells, which was hypothesized from the systemic pharmacological analysis of ASF, focusing on the combined effect of ASF extract (ASFE) and imatinib (IM). e compounds of ASF were identified using the Traditional Chinese Medicine Systems Pharmacology database and analysis platform. e target gene information was acquired from the UniProt database. e compound and target interaction network was generated from Cytoscape 3.7.1. Using this analysis, 10 compounds effective against CML cells were obtained. ASFE was prepared and analyzed by high-pressure liquid chromatography to provide experimental proof for the relationship between ASF and CML. e anti-p210 Bcr-Abl effects of ASFE and ASFE + IM combination were evaluated by western blotting. Either ASFE alone or in combined treatment with IM on K-562 CML cells resulted in a significant reduction of the Bcr-Abl levels. As expected from the systemic analysis results, ASF had antileukemic activity, showing that it is a potential therapy for CML.

show abstract

Astragalin inhibits autophagy-associated airway epithelial fibrosis

Cited by 62 publications

References 32 publications

Autophagy in airway diseases: a new frontier in human asthma?

Autophagy in airway diseases: a new frontier in human asthma?

TP53-dependent autophagy links the ATR-CHEK1 axis activation to proinflammatory VEGFA production in human bronchial epithelial cells exposed to fine particulate matter (PM2.5)

Systemic Pharmacological Approach to Identification and Experimental Verification of the Effect of Anisi Stellati Fructus Extract on Chronic Myeloid Leukemia Cells

Contact Info

Product

Resources

About