A1 Refereed original research article in a scientific journal
Body-wide genetic deficiency of poly(ADP-ribose) polymerase 14 sensitizes mice to colitis
Authors: Vedantham, Madhukar; Polari, Lauri; Poosakkannu, Anbu; Pinto, Rita G.; Sakari, Moona; Laine, Jukka; Sipilä, Petra; Määttä, Jorma; Gerke, Heidi; Rissanen, Tiia; Rantakari, Pia; Toivola, Diana M.; Pulliainen, Arto T.
Publisher: John Wiley & Sons
Publication year: 2024
Journal: FASEB Journal
Journal name in source: FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Journal acronym: FASEB J
Article number: e23775
Volume: 38
Issue: 13
ISSN: 0892-6638
eISSN: 1530-6860
DOI: https://doi.org/10.1096/fj.202400484R
Web address : https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202400484R
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/457135692
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.
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Funding information in the publication:
This work was financially supported by Research Council of Finland grants with project numbers 295296 and 329252 to ATP as well as 315139 and 332582 (including InFLAMES Flagship Programme, 337531 and 357911) to DMT and the 1-year Finnish Cultural Foundation personal grant 00231206 to MV. In addition, MV has received a 2-year salary package from the Turku Doctoral Programme of Molecular Medicine (TuDMM). Mika Savisalo, Merja Lakkisto, and personnel of the Histology core facility (Institute of Biomedicine, University of Turku, Turku, Finland) are acknowledged for technical support.
