Role of poly(ADP-ribose) glycohydrolase in the development of inflammatory bowel disease in mice.

摘要: Abstract Poly(ADP-ribose) is synthesized from nicotinamide adenine dinucleotide (NAD) by poly(ADP-ribose) polymerase 1 (PARP-1) and degraded glycohydrolase (PARG). The aim of the present study was to examine role PARG in development experimental colitis. To address this question, we used an model colitis, induced dinitrobenzene sulfonic acid (DNBS). Mice lacking functional 110-kDa isoform (PARG110KO mice) were resistant colon injury DNBS. mucosa tissues showed reduction myeloperoxidase activity attenuated staining for intercellular adhesion molecule vascular cell 1. Moreover, overproduction proinflammatory factors TNF-α IL-1β activation death signaling pathway, i.e., FAS ligand, inhibited these mutant mice. Finally pharmacological treatment WT mice with GPI 16552 18214, two novel inhibitors, a significant protective effect DNBS-induced These genetic studies demonstrate that modulates inflammatory response tissue events associated colitis may be considered as target intervention pathogenesis.