Reduced Colonic Mucosal Injury in 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Poly ADP-Ribose Polymerase (TIPARP/PARP7)-Deficient Mice.

Abstract

Poly-ADP-ribose polymerases (PARPs) are important regulators of the immune system, including TCDD-inducible poly-ADP-ribose polymerase (TIPARP), also known as poly-ADP-ribose polymerase 7 (PARP7). PARP7 negatively regulates aryl hydrocarbon receptor (AHR) and type I interferon (IFN-I) signaling, both of which have been implicated in intestinal homeostasis and immunity. Since the loss of PARP7 expression increases AHR and IFN-I signaling, we used a murine dextran sulfate sodium (DSS)-induced colitis model to investigate the effect of PARP7 loss on DSS-induced intestinal inflammation. DSS-exposed Parp7-/- mice had less body weight loss, lower disease index scores, and reduced expression of several inflammation genes, including interleukin IL-6, C-x-c motif chemokine ligand 1 (Cxcl1), and lipocalin-2, when compared with wild-type mice. However, no significant difference was observed between genotypes in the colonic expression of the AHR target gene cytochrome P450 1A1 (Cyp1a1). Moreover, no significant differences in microbial composition were observed between the genotypes. Our findings demonstrate that the absence of PARP7 protein results in an impaired immune response to colonic inflammation and suggests that PARP7 may participate in the recruitment of immune cells to the inflammation site, which may be due to its role in IFN-I signaling rather than AHR signaling.

• Authors: David Hutin, Karoline Alvik Hagen, Peng Shao, Kim Sugamori, Denis M Grant, Jason Matthews
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 23 Issue 2 (Jan 15 2022) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 35055106 (Publication Type: Journal Article)

Chemical References

• Ahr protein, mouse
• Basic Helix-Loop-Helix Transcription Factors
• Chemokine CXCL1
• Cxcl1 protein, mouse
• Interferon Type I
• Interleukin-6
• Lipocalin-2
• Receptors, Aryl Hydrocarbon
• interleukin-6, mouse
• Dextran Sulfate
• Cyp1a1 protein, mouse
• Cytochrome P-450 CYP1A1
• ADP Ribose Transferases
• Parp7 protein, mouse

Topics

• ADP Ribose Transferases (genetics)
• Animals
• Basic Helix-Loop-Helix Transcription Factors (metabolism)
• Chemokine CXCL1 (genetics)
• Colitis (chemically induced, genetics, pathology)
• Cytochrome P-450 CYP1A1 (genetics)
• Dextran Sulfate (adverse effects)
• Disease Models, Animal
• Fibroblasts (chemistry, cytology)
• Gene Knockout Techniques
• Interferon Type I (metabolism)
• Interleukin-6 (genetics)
• Lipocalin-2 (genetics)
• Male
• Mice
• Receptors, Aryl Hydrocarbon (metabolism)
• Signal Transduction
• Up-Regulation