Astragalus polysaccharide protects experimental colitis through an aryl hydrocarbon receptor-dependent autophagy mechanism.
Astragalus polysaccharide
aryl hydrocarbon receptor
autophagy
experimental colitis
Journal
British journal of pharmacology
ISSN: 1476-5381
Titre abrégé: Br J Pharmacol
Pays: England
ID NLM: 7502536
Informations de publication
Date de publication:
31 Aug 2023
31 Aug 2023
Historique:
revised:
17
08
2023
received:
08
02
2023
accepted:
21
08
2023
pubmed:
1
9
2023
medline:
1
9
2023
entrez:
1
9
2023
Statut:
aheadofprint
Résumé
Disruption of intestinal barriers plays a vital role in the pathogenesis of colitis. The aryl hydrocarbon receptor (AhR) is a recognition sensor that mediates intestinal immune homeostasis and minimizes intestinal inflammation. Astragalus polysaccharide (APS) exerts pharmacological actions in colitis; however, the mechanism has not been elucidated. We investigated whether APS protects through AhR-dependent autophagy. The symptoms of dextran sulfate sodium (DSS)-induced colitis in mice involving intestinal barrier function and inflammatory injury were evaluated after APS administration. Intestinal-specific Becn1 conditional knockout (Becn1 cKO) mice were constructed and compared with wild-type mice. Autophagy and the effects of APS were investigated after the deactivation of AhRs. The relationship between APS-induced AhRs and autophagic Becn1 was investigated using a dual-luciferase reporter system and chromatin immunoprecipitation (ChIP)-quantitative polymerase chain reaction assay. Caco-2 cells were used to investigate inflammatory responses and AhR-dependent autophagy. APS improved intestinal barrier function in inflammatory injury in colitis mice. APS triggered autophagic flow; however, knockout of Becn1 in the gut increased susceptibility to colitis, leading to diminished epithelial barrier function and severe intestinal inflammation, impairing the protective effects of APS. Mechanistically, APS-triggered autophagy depends on AhR expression. Activated AhR binds to the promoter Becn1 to operate transcription of genes involved in anti-inflammation and intestinal barrier repair, while deactivation of AhR correlated with intestinal inflammation and the therapeutic function of APS. APS protects colitis mice by targeting autophagy, especially as the AhR stimulates the repair of damaged intestinal barrier functions.
Sections du résumé
BACKGROUND AND PURPOSE
OBJECTIVE
Disruption of intestinal barriers plays a vital role in the pathogenesis of colitis. The aryl hydrocarbon receptor (AhR) is a recognition sensor that mediates intestinal immune homeostasis and minimizes intestinal inflammation. Astragalus polysaccharide (APS) exerts pharmacological actions in colitis; however, the mechanism has not been elucidated. We investigated whether APS protects through AhR-dependent autophagy.
EXPERIMENTAL APPROACH
METHODS
The symptoms of dextran sulfate sodium (DSS)-induced colitis in mice involving intestinal barrier function and inflammatory injury were evaluated after APS administration. Intestinal-specific Becn1 conditional knockout (Becn1 cKO) mice were constructed and compared with wild-type mice. Autophagy and the effects of APS were investigated after the deactivation of AhRs. The relationship between APS-induced AhRs and autophagic Becn1 was investigated using a dual-luciferase reporter system and chromatin immunoprecipitation (ChIP)-quantitative polymerase chain reaction assay. Caco-2 cells were used to investigate inflammatory responses and AhR-dependent autophagy.
KEY RESULTS
RESULTS
APS improved intestinal barrier function in inflammatory injury in colitis mice. APS triggered autophagic flow; however, knockout of Becn1 in the gut increased susceptibility to colitis, leading to diminished epithelial barrier function and severe intestinal inflammation, impairing the protective effects of APS. Mechanistically, APS-triggered autophagy depends on AhR expression. Activated AhR binds to the promoter Becn1 to operate transcription of genes involved in anti-inflammation and intestinal barrier repair, while deactivation of AhR correlated with intestinal inflammation and the therapeutic function of APS.
CONCLUSIONS AND IMPLICATIONS
CONCLUSIONS
APS protects colitis mice by targeting autophagy, especially as the AhR stimulates the repair of damaged intestinal barrier functions.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Natural Science Foundation of China
ID : 31860274
Organisme : National Natural Science Foundation of China
ID : 81860646
Organisme : Yunnan Provincial Science and Technology Department
ID : 2019FI016
Organisme : Yunnan Provincial Science and Technology Department
ID : 202005AC160058
Organisme : Yunnan Provincial Science and Technology Department
ID : 202101AZ070001-012
Organisme : Yunnan Provincial Science and Technology Department
ID : 202201AS070084
Informations de copyright
© 2023 British Pharmacological Society.
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