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Body-wide genetic deficiency of poly(ADP-ribose) polymerase 14 sensitizes mice to colitis.
- Source :
-
FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2024 Jul 15; Vol. 38 (13), pp. e23775. - Publication Year :
- 2024
-
Abstract
- Inflammatory bowel disease (IBD) is a chronic disease of the gastrointestinal tract affecting millions of people. Here, we investigated the expression and functions of poly(ADP-ribose) polymerase 14 (Parp14), an important regulatory protein in immune cells, with an IBD patient cohort as well as two mouse colitis models, that is, IBD-mimicking oral dextran sulfate sodium (DSS) exposure and oral Salmonella infection. Parp14 was expressed in the human colon by cells in the lamina propria, but, in particular, by the epithelial cells with a granular staining pattern in the cytosol. The same expression pattern was evidenced in both mouse models. Parp14-deficiency caused increased rectal bleeding as well as stronger epithelial erosion, Goblet cell loss, and immune cell infiltration in DSS-exposed mice. The absence of Parp14 did not affect the mouse colon bacterial microbiota. Also, the colon leukocyte populations of Parp14-deficient mice were normal. In contrast, bulk tissue RNA-Seq demonstrated that the colon transcriptomes of Parp14-deficient mice were dominated by abnormalities in inflammation and infection responses both prior and after the DSS exposure. Overall, the data indicate that Parp14 has an important role in the maintenance of colon epithelial barrier integrity. The prognostic and predictive biomarker potential of Parp14 in IBD merits further investigation.<br /> (© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)
- Subjects :
- Animals
Female
Humans
Male
Mice
Colon pathology
Colon metabolism
Disease Models, Animal
Gastrointestinal Microbiome
Inflammatory Bowel Diseases genetics
Inflammatory Bowel Diseases pathology
Inflammatory Bowel Diseases metabolism
Mice, Knockout
Colitis genetics
Colitis chemically induced
Colitis pathology
Dextran Sulfate toxicity
Mice, Inbred C57BL
Poly(ADP-ribose) Polymerases metabolism
Poly(ADP-ribose) Polymerases genetics
Poly(ADP-ribose) Polymerases deficiency
Subjects
Details
- Language :
- English
- ISSN :
- 1530-6860
- Volume :
- 38
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology
- Publication Type :
- Academic Journal
- Accession number :
- 38967223
- Full Text :
- https://doi.org/10.1096/fj.202400484R