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Akkermansia muciniphila ameliorates colonic injury in mice with DSS-induced acute colitis by blocking macrophage pro-inflammatory phenotype switching via the HDAC5/DAB2 axis.
- Source :
-
Biochimica et biophysica acta. Molecular cell research [Biochim Biophys Acta Mol Cell Res] 2024 Oct; Vol. 1871 (7), pp. 119751. Date of Electronic Publication: 2024 May 21. - Publication Year :
- 2024
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Abstract
- Akkermansia muciniphila (A. muciniphila), a probiotic, has been linked to macrophage phenotypic polarization in different diseases. However, the role and mechanisms of A. muciniphila in regulating macrophage during ulcerative colitis (UC) are not clear. This research aimed to examine the impact of A. muciniphila on dextran sulfate sodium (DSS)-induced acute colitis and elucidate the underlying mechanism related to macrophage phenotypic polarization. A. muciniphila inhibited weight loss, increased disease activity index, and ameliorated inflammatory injury in colonic tissues in mice induced with DSS. Furthermore, A. muciniphila reduced macrophage M1 polarization and ameliorated epithelial barrier damage in colonic tissues of DSS-induced mice through inhibition of histone deacetylase 5 (HDAC5). In contrast, the effect of A. muciniphila was compromised by HDAC5 overexpression. HDAC5 deacetylated H3K9ac modification of the disabled homolog 2 (DAB2) promoter, which led to repressed DAB2 expression. DAB2 overexpression blocked HDAC5-induced pro-inflammatory polarization of macrophages, whereas knockdown of DAB2 resulted in the loss of effects of A. muciniphila against colonic injury in DSS-induced mice. Taken together, A. muciniphila-induced loss of HDAC5 hampered the deacetylation of DAB2 and enhanced the expression of DAB2. Our findings propose that A. muciniphila may be a possible probiotic agent for alleviating DSS-induced acute colitis.<br />Competing Interests: Declaration of competing interest The authors declare that they have no competing interests.<br /> (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Mice
Probiotics administration & dosage
Adaptor Proteins, Signal Transducing genetics
Adaptor Proteins, Signal Transducing metabolism
Mice, Inbred C57BL
Phenotype
Colon pathology
Colon metabolism
Colon microbiology
Male
Disease Models, Animal
Inflammation metabolism
Inflammation pathology
Dextran Sulfate toxicity
Histone Deacetylases metabolism
Histone Deacetylases genetics
Macrophages metabolism
Akkermansia
Colitis chemically induced
Colitis metabolism
Colitis pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-2596
- Volume :
- 1871
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Biochimica et biophysica acta. Molecular cell research
- Publication Type :
- Academic Journal
- Accession number :
- 38776988
- Full Text :
- https://doi.org/10.1016/j.bbamcr.2024.119751